首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1220655367277695328, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1220655362521351042, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2020-0698, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1588867200000, receivedDateStr=2020-05-08, revisedDate=1591372800000, revisedDateStr=2020-06-06, acceptedDate=null, acceptedDateStr=null, onlineDate=1768956518239, onlineDateStr=2026-01-21, pubDate=1594483200000, pubDateStr=2020-07-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1768956518239, onlineIssueDateStr=2026-01-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1768956518239, creator=13701087609, updateTime=1768956518239, updator=13701087609, issue=Issue{id=1220655362521351042, tenantId=1146029695717560320, journalId=1189982191388893191, year='2020', volume='55', issue='7', pageStart='1357', pageEnd='1706', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1768956517105, creator=13701087609, updateTime=1768957228011, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1220658344335950505, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1220655362521351042, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1220658344335950506, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1220655362521351042, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1691, endPage=1698, ext={EN=ArticleExt(id=1220655367743263106, articleId=1220655367277695328, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Hetero-biosynthesis of the main bioactive components from medicinal fungus Shiraia bambusiccola, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

Shiraia bambusiccola is an important medicinal fungus in China. Hypocrellins with perylenequinone skeleton are main bioactive components of Shiraia bambusiccola, which are widely used in food, medicine, pesticide and other fields as natural photosensitizers. For example, "hypocrellin ointment" has already been used clinically. As a rare and vulnerable species, wild Shiraia bambusiccola resources are very limited. Due to the complex structure and chanllenge in chemical total synthesis of hypocrellins, it is urgent to find an effective strategy to rationally utilize its medicinal value while protecting the wild resources. In this study, a candidate gene cluster hpc was identified in Shiraia sp. cfcc 84681 based on careful bioinformatic analysis. A heterologous expression system for hpc gene cluster was successfully constructed and a mutant strain with high yield of hypocrellins was obtained, which mainly produced hypocrellin A and isohypocrellin A. The main ingredients in the mutant strain are consistent with that in the wild Shiraia bambusiccola. These results provide a new strategy to solve the shortage of wild Shiraia bambusiccola resources.

, correspAuthors=You-cai HU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2020 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Ya-long ZHANG, Le ZHANG, Jie GAO, Jian BAI, Dao-jiang YAN, Yuan-yuan ZHANG, You-cai HU), CN=ArticleExt(id=1220655369035108827, articleId=1220655367277695328, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=药用真菌竹黄主要活性成分的异源生物合成, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

竹黄是我国一种重要的药用真菌资源，其主要活性成分竹红菌素类化合物已作为天然光敏剂广泛应用于食品、医药、农药等领域，其中竹红菌素软膏已用于临床。然而作为一种珍稀易危的物种，野生竹黄的资源非常有限。而竹红菌素结构复杂化学合成成本高，因此亟待一种有效的方法在保护竹黄野生资源的同时合理利用其药用价值。本文即采用合成生物学技术来获取竹黄中的主要活性成分，以期摆脱对野生资源的依赖。通过对竹黄菌Shiraia sp.cfcc 84681的全基因组进行细致的生物信息学分析，从中挖掘到一条竹红菌素生物合成的候选基因簇hpc；并成功构建了该基因簇的异源表达系统，获得一株产竹红菌素类化合物的重组菌株。该菌株主要产竹红菌甲素和异竹红菌甲素，这与野生竹黄提取物的主要成分基本一致。本研究有望为解决野生竹黄的资源短缺问题提供一种新的有效途径。

, correspAuthors=胡友财, authorNote=null, correspAuthorsNote=
*胡友财, E-mail:
, copyrightStatement=版权所有©《药学学报》编辑部2020, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=m+Phtkqn48q6gkBOSqniTA==, magXml=xNWLR4EwKc8tnS3DCczvZw==, pdfUrl=null, pdf=O9rsUbI7VmhT2EKrO7EO9Q==, pdfFileSize=612117, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=3NIo3UzvxaJGYJf+CKdUyw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=48mJsKPnFVaEoJICxF8c5Q==, mapNumber=null, authorCompany=null, fund=null, authors=

#共同第一作者

, authorsList=张亚龙, 张乐, 高洁, 柏健, 闫道江, 张元元, 胡友财)}, authors=[Author(id=1220655369571979772, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1220655369685225991, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655369571979772, language=EN, stringName=Ya-long ZHANG, firstName=Ya-long, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655369806860816, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655369571979772, language=CN, stringName=张亚龙, firstName=亚龙, middleName=null, lastName=张, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, #, address=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)])]), Author(id=1220655369949467165, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1220655370083684904, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655369949467165, language=EN, stringName=Le ZHANG, firstName=Le, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655370154988079, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655369949467165, language=CN, stringName=张乐, firstName=乐, middleName=null, lastName=张, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, #, address=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)])]), Author(id=1220655370276622904, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1220655370385674813, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655370276622904, language=EN, stringName=Jie GAO, firstName=Jie, middleName=null, lastName=GAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655370473755202, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655370276622904, language=CN, stringName=高洁, firstName=洁, middleName=null, lastName=高, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)])]), Author(id=1220655370561835594, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1220655370670887507, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655370561835594, language=EN, stringName=Jian BAI, firstName=Jian, middleName=null, lastName=BAI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655370796716633, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655370561835594, language=CN, stringName=柏健, firstName=健, middleName=null, lastName=柏, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)])]), Author(id=1220655370880602720, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1220655370964488805, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655370880602720, language=EN, stringName=Dao-jiang YAN, firstName=Dao-jiang, middleName=null, lastName=YAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655371048374891, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655370880602720, language=CN, stringName=闫道江, firstName=道江, middleName=null, lastName=闫, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)])]), Author(id=1220655371132260978, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1220655371241312886, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655371132260978, language=EN, stringName=Yuan-yuan ZHANG, firstName=Yuan-yuan, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2. School of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655371350364799, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655371132260978, language=CN, stringName=张元元, firstName=元元, middleName=null, lastName=张, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.沈阳药科大学中药学院, 辽宁 沈阳 110016, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369433567730, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369437762034, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369433567730, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. School of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China), AuthorCompanyExt(id=1220655369446150644, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369433567730, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.沈阳药科大学中药学院, 辽宁 沈阳 110016)])]), Author(id=1220655371442639494, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, orderNo=6, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=huyoucai@imm.ac.cn, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1220655371551691404, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655371442639494, language=EN, stringName=You-cai HU, firstName=You-cai, middleName=null, lastName=HU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, *, address=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1220655371643966100, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, authorId=1220655371442639494, language=CN, stringName=胡友财, firstName=友财, middleName=null, lastName=胡, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, *, address=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)])])], keywords=[Keyword(id=1220655371753018012, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, orderNo=1, keyword=medicinal fungus), Keyword(id=1220655371849487010, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, orderNo=2, keyword=Shiraia bambusiccola), Keyword(id=1220655371941761703, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, orderNo=3, keyword=hypocrellin), Keyword(id=1220655372042425003, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, orderNo=4, keyword=hetero-biosynthesis), Keyword(id=1220655372138894002, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, orderNo=5, keyword=synthetic biology), Keyword(id=1220655372222780084, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, orderNo=1, keyword=药用真菌), Keyword(id=1220655372331831995, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, orderNo=2, keyword=竹黄), Keyword(id=1220655372424106686, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, orderNo=3, keyword=竹红菌素), Keyword(id=1220655372533158595, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, orderNo=4, keyword=异源生物合成), Keyword(id=1220655372608656068, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, orderNo=5, keyword=合成生物学)], refs=[Reference(id=1220655374743556884, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2008, volume=27, issue=null, pageStart=21, pageEnd=26, url=http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=wxqgdxxb200805004, language=null, rfNumber=[1], rfOrder=0, authorNames=Liang XH, Cai YJ, Liao XR, journalName=J Food Sci Biotechnol (食品与生物技术学报), refType=null, unstructuredReference= Liang XH , Cai YJ , Liao XR et al . The progress of research on medicinal fungus Shiraia bambusicola[J]. J Food Sci Biotechnol (食品与生物技术学报), 2008, 27: 21-26., articleTitle=The progress of research on medicinal fungus Shiraia bambusicola, refAbstract=null), Reference(id=1220655374840025880, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2002, volume=33, issue=null, pageStart=372, pageEnd=374, url=http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zcy200204041, language=null, rfNumber=[2], rfOrder=1, authorNames=Zhong SR, Zhao H, Li AM, journalName=Chin Tradit Herb Drugs (中草药), refType=null, unstructuredReference= Zhong SR , Zhao H , Li AM et al . Potential TCM-Shiraia bambusicola[J]. Chin Tradit Herb Drugs (中草药), 2002, 33: 372-374., articleTitle=Potential TCM-Shiraia bambusicola, refAbstract=null), Reference(id=1220655374928106268, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2000, volume=19, issue=null, pageStart=8, pageEnd=11, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=Lai GH, Fu LY, journalName=Chin Wild Plant Resour (中国野生植物资源), refType=null, unstructuredReference= Lai GH , Fu LY . Study on the main host plants of Shiraia bambusicola[J]. Chin Wild Plant Resour (中国野生植物资源), 2000, 19: 8-11., articleTitle=Study on the main host plants of Shiraia bambusicola, refAbstract=null), Reference(id=1220655375041352481, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2006, volume=33, issue=null, pageStart=147, pageEnd=150, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=Jia XM, Xu XH, Zhuang BC, journalName=Microbiol China (微生物学通报), refType=null, unstructuredReference= Jia XM , Xu XH , Zhuang BC et al . The progress of biological reasearch of medicinal fungus Shirar bambusicola[J]. Microbiol China (微生物学通报), 2006, 33: 147-150., articleTitle=The progress of biological reasearch of medicinal fungus Shirar bambusicola, refAbstract=null), Reference(id=1220655375133627173, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2017, volume=8, issue=null, pageStart=108, pageEnd=109, url=http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgwsbzgl201720057, language=null, rfNumber=[5], rfOrder=4, authorNames=Cui LQ, journalName=China Health Standard Manag (中国卫生标准管理), refType=null, unstructuredReference= Cui LQ . Investigate the clinical value of bamboo mushroom ointment in the treatment of leukoplakia[J]. China Health Standard Manag (中国卫生标准管理), 2017, 8: 108-109., articleTitle=Investigate the clinical value of bamboo mushroom ointment in the treatment of leukoplakia, refAbstract=null), Reference(id=1220655375246873387, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1111/j.1751-1097.1990.tb01807.x, pmid=null, pmcid=null, year=1990, volume=52, issue=null, pageStart=609, pageEnd=616, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=Zhenjun D, Lown JW, journalName=Photochem Photobiol, refType=null, unstructuredReference= Zhenjun D , Lown JW . Hypocrellins and their use in photosensitization[J]. Photochem Photobiol, 1990, 52: 609-616., articleTitle=Hypocrellins and their use in photosensitization, refAbstract=null), Reference(id=1220655375351730991, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=1987, volume=52, issue=null, pageStart=1, pageEnd=71, url=https://link.springer.com/chapter/10.1007%2F978-3-7091-8906-1_1, language=null, rfNumber=[7], rfOrder=6, authorNames=Weiss U, Merlini L, Nasini G, journalName=Fortschr Chem Org Naturst, refType=null, unstructuredReference= Weiss U , Merlini L , Nasini G . Naturally occurring perylenequinones[J]. Fortschr Chem Org Naturst, 1987, 52: 1-71., articleTitle=Naturally occurring perylenequinones, refAbstract=null), Reference(id=1220655375435617075, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1111/j.1751-1097.1998.tb03251.x, pmid=null, pmcid=null, year=1998, volume=68, issue=null, pageStart=44, pageEnd=50, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=Chaloupka R, Sureau F, Kocisova E, journalName=Photochem Photobiol, refType=null, unstructuredReference= Chaloupka R , Sureau F , Kocisova E et al . Hypocrellin A photosensitization involves an intracellular pH decrease in 3T3 cells[J]. Photochem Photobiol, 1998, 68: 44-50., articleTitle=Hypocrellin A photosensitization involves an intracellular pH decrease in 3T3 cells, refAbstract=null), Reference(id=1220655375532086069, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1016/j.msec.2019.110230, pmid=null, pmcid=null, year=2020, volume=106, issue=null, pageStart=110230, pageEnd=110241, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=Guo LY, Yan SZ, Tao X, journalName=Mater Sci Eng C Mater Biol Appl, refType=null, unstructuredReference= Guo LY , Yan SZ , Tao X et al . Evaluation of hypocrellin a-loaded lipase sensitive polymer micelles for intervening methicillin-resistant Staphylococcus aureus antibiotic-resistant bacterial infection[J]. Mater Sci Eng C Mater Biol Appl, 2020, 106: 110230-110241., articleTitle=Evaluation of hypocrellin a-loaded lipase sensitive polymer micelles for intervening methicillin-resistant Staphylococcus aureus antibiotic-resistant bacterial infection, refAbstract=null), Reference(id=1220655375645332280, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1055/s-2006-960121, pmid=null, pmcid=null, year=1991, volume=57, issue=null, pageStart=376, pageEnd=379, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=Kishi T, Tahara S, Taniguchi N, journalName=Planta Med, refType=null, unstructuredReference= Kishi T , Tahara S , Taniguchi N et al . New perylenequinones from Shiraia bambusicola[J]. Planta Med, 1991, 57: 376-379., articleTitle=New perylenequinones from Shiraia bambusicola, refAbstract=null), Reference(id=1220655375733412667, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2012, volume=21, issue=null, pageStart=3887, pageEnd=3904, url=https://pubmed.ncbi.nlm.nih.gov/24039544/, language=null, rfNumber=[11], rfOrder=10, authorNames=Mulrooey CA, O'Brien EM, Morgan BJ, journalName=Eur J Org Chem, refType=null, unstructuredReference= Mulrooey CA , O'Brien EM , Morgan BJ et al . Perylenequinones:isolation, synthesis, and biological activity[J]. Eur J Org Chem, 2012, 21: 3887-3904., articleTitle=Perylenequinones:isolation, synthesis, and biological activity, refAbstract=null), Reference(id=1220655375855047487, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1002/anie.200800734, pmid=null, pmcid=null, year=2008, volume=47, issue=null, pageStart=6877, pageEnd=6880, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=O'Brien EM, Morgan BJ, Kozlowski MC, journalName=Angew Chem Int Ed, refType=null, unstructuredReference= O'Brien EM , Morgan BJ , Kozlowski MC . Dynamic stereochemistry transfer in a transannular aldol reaction:total synthesis of hypocrellin A[J]. Angew Chem Int Ed, 2008, 47: 6877-6880., articleTitle=Dynamic stereochemistry transfer in a transannular aldol reaction:total synthesis of hypocrellin A, refAbstract=null), Reference(id=1220655375968293699, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1021/jo901386d, pmid=null, pmcid=null, year=2010, volume=75, issue=null, pageStart=57, pageEnd=68, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=O'Brien EM, Morgan BJ, Mulrooney CA, journalName=J Org Chem, refType=null, unstructuredReference= O'Brien EM , Morgan BJ , Mulrooney CA et al . Perylenequinone natural products:total synthesis of hypocrellin A[J]. J Org Chem, 2010, 75: 57-68., articleTitle=Perylenequinone natural products:total synthesis of hypocrellin A, refAbstract=null), Reference(id=1220655376068956999, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1021/ja902324j, pmid=null, pmcid=null, year=2009, volume=131, issue=null, pageStart=9413, pageEnd=9425, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=Morgan BJ, Dey S, Johnson SW, journalName=J Am Chem Soc, refType=null, unstructuredReference= Morgan BJ , Dey S , Johnson SW et al . Design, synthesis, and investigation of protein kinase C inhibitors:total syntheses of (+)-calphostin D, (+)-phleichrome, cercosporin, and new photoactive perylenequinones[J]. J Am Chem Soc, 2009, 131: 9413-9425., articleTitle=Design, synthesis, and investigation of protein kinase C inhibitors:total syntheses of (+)-calphostin D, (+)-phleichrome, cercosporin, and new photoactive perylenequinones, refAbstract=null), Reference(id=1220655376182203211, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1038/nature10403, pmid=null, pmcid=null, year=2011, volume=477, issue=null, pageStart=471, pageEnd=476, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=Dymond JS, Richardson SM, Coombes CE, journalName=Nature, refType=null, unstructuredReference= Dymond JS , Richardson SM , Coombes CE et al . Synthetic chromosome arms function in yeast and generate phenotypic diversity by design[J]. Nature, 2011, 477: 471-476., articleTitle=Synthetic chromosome arms function in yeast and generate phenotypic diversity by design, refAbstract=null), Reference(id=1220655376308032335, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1038/nature12051, pmid=null, pmcid=null, year=2013, volume=496, issue=null, pageStart=528, pageEnd=532, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=Paddon CJ, Westfall PJ, Pitera DJ, journalName=Nature, refType=null, unstructuredReference= Paddon CJ , Westfall PJ , Pitera DJ et al . High-level semi-synthetic production of the potent antimalarial artemisinin[J]. Nature, 2013, 496: 528-532., articleTitle=High-level semi-synthetic production of the potent antimalarial artemisinin, refAbstract=null), Reference(id=1220655376438055762, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1371/journal.pone.0196519, pmid=null, pmcid=null, year=2018, volume=13, issue=null, pageStart=e0196519, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=Gao RJ, Xu ZC, Deng HX, journalName=PLoS One, refType=null, unstructuredReference= Gao RJ , Xu ZC , Deng HX et al . Enhanced hypocrellin production of Shiraia sp. SUPER-H168 by overexpression of alpha-amylase gene[J]. PLoS One, 2018, 13: e0196519., articleTitle=Enhanced hypocrellin production of Shiraia sp. SUPER-H168 by overexpression of alpha-amylase gene, refAbstract=null), Reference(id=1220655376542913364, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1186/s13568-018-0597-0, pmid=null, pmcid=null, year=2018, volume=8, issue=null, pageStart=71, pageEnd=81, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=Gao RJ, Deng HX, Guan ZB, journalName=AMB Express, refType=null, unstructuredReference= Gao RJ , Deng HX , Guan ZB et al . Enhanced hypocrellin production via coexpression of alpha-amylase and hemoglobin genes in Shiraia Bambusicola[J]. AMB Express, 2018, 8: 71-81., articleTitle=Enhanced hypocrellin production via coexpression of alpha-amylase and hemoglobin genes in Shiraia Bambusicola, refAbstract=null), Reference(id=1220655376656159576, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1007/s12010-009-8728-3, pmid=null, pmcid=null, year=2010, volume=160, issue=null, pageStart=2275, pageEnd=2286, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=Cai YJ, Liang XH, Liao XR, journalName=Appl Biochem Biotechnol, refType=null, unstructuredReference= Cai YJ , Liang XH , Liao XR et al . High-yield hypocrellin A production in solid-state fermentation by Shiraia sp. SUPER-H168[J]. Appl Biochem Biotechnol, 2010, 160: 2275-2286., articleTitle=High-yield hypocrellin A production in solid-state fermentation by Shiraia sp. SUPER-H168, refAbstract=null), Reference(id=1220655376761017180, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1007/s00203-018-1529-8, pmid=null, pmcid=null, year=2018, volume=200, issue=null, pageStart=1217, pageEnd=1225, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=Gao RJ, Xu ZC, Deng HX, journalName=Arch Microbiol, refType=null, unstructuredReference= Gao RJ , Xu ZC , Deng HX et al . Influences of light on growth, reproduction and hypocrellin production by Shiraia sp. SUPER-H168[J]. Arch Microbiol, 2018, 200: 1217-1225., articleTitle=Influences of light on growth, reproduction and hypocrellin production by Shiraia sp. SUPER-H168, refAbstract=null), Reference(id=1220655376870069087, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1099/mic.0.2007/007294-0, pmid=null, pmcid=null, year=2007, volume=153, issue=null, pageStart=2781, pageEnd=2790, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=Chen HQ, Lee MH, Chung KR, journalName=Microbiology, refType=null, unstructuredReference= Chen HQ , Lee MH , Chung KR . Functional characterization of three genes encoding putative oxidoreductases required for cercosporin toxin biosynthesis in the fungus Cercospora nicotianae[J]. Microbiology, 2007, 153: 2781-2790., articleTitle=Functional characterization of three genes encoding putative oxidoreductases required for cercosporin toxin biosynthesis in the fungus Cercospora nicotianae, refAbstract=null), Reference(id=1220655376949760865, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1021/jacs.6b00633, pmid=null, pmcid=null, year=2016, volume=138, issue=null, pageStart=4219, pageEnd=4228, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=Newman AG, Townsend CA, journalName=J Am Chem Soc, refType=null, unstructuredReference= Newman AG , Townsend CA . Molecular characterization of the cercosporin biosynthetic pathway in the fungal plant pathogen Cercospora nicotianae[J]. J Am Chem Soc, 2016, 138: 4219-4228., articleTitle=Molecular characterization of the cercosporin biosynthetic pathway in the fungal plant pathogen Cercospora nicotianae, refAbstract=null), Reference(id=1220655377012675429, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2014, volume=2, issue=null, pageStart=e00011, pageEnd=e00014, url=https://pubmed.ncbi.nlm.nih.gov/24503982/, language=null, rfNumber=[23], rfOrder=22, authorNames=Yang H, Wang Y, Zhang Z, journalName=Genome Announc, refType=null, unstructuredReference= Yang H , Wang Y , Zhang Z et al . Whole-genome shotgun assembly and analysis of the genome of Shiraia sp. strain Slf14, a novel endophytic fungus producing huperzine A and hypocrellin A[J]. Genome Announc, 2014, 2: e00011-e00014., articleTitle=Whole-genome shotgun assembly and analysis of the genome of Shiraia sp. strain Slf14, a novel endophytic fungus producing huperzine A and hypocrellin A, refAbstract=null), Reference(id=1220655377117533033, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1111/1462-2920.13711, pmid=null, pmcid=null, year=2017, volume=19, issue=null, pageStart=1975, pageEnd=1986, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=Chooi YH, Zhang G, Hu J, journalName=Environ Microbiol, refType=null, unstructuredReference= Chooi YH , Zhang G , Hu J et al . Functional genomics-guided discovery of a light-activated phytotoxin in the wheat pathogen Parastagonospora nodorum via pathway activation[J]. Environ Microbiol, 2017, 19: 1975-1986., articleTitle=Functional genomics-guided discovery of a light-activated phytotoxin in the wheat pathogen Parastagonospora nodorum via pathway activation, refAbstract=null), Reference(id=1220655377201419117, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=null, pmid=null, pmcid=null, year=2018, volume=10, issue=null, pageStart=1457, pageEnd=1465, url=https://pubmed.ncbi.nlm.nih.gov/30809363/, language=null, rfNumber=[25], rfOrder=24, authorNames=Hu J, Sarrami F, Li H, journalName=Chem Sci, refType=null, unstructuredReference= Hu J , Sarrami F , Li H et al . Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system[J]. Chem Sci, 2018, 10: 1457-1465., articleTitle=Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system, refAbstract=null), Reference(id=1220655377297888114, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1038/ja.2006.49, pmid=null, pmcid=null, year=2006, volume=59, issue=null, pageStart=351, pageEnd=354, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=Fang LZ, Qing C, Shao HJ, journalName=J Antibiot, refType=null, unstructuredReference= Fang LZ , Qing C , Shao HJ et al . Hypocrellin D, a cytotoxic fungal pigment from fruiting bodies of the ascomycete Shiraia bambusicola[J]. J Antibiot, 2006, 59: 351-354., articleTitle=Hypocrellin D, a cytotoxic fungal pigment from fruiting bodies of the ascomycete Shiraia bambusicola, refAbstract=null), Reference(id=1220655377398551414, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, doi=10.1007/s10295-013-1386-z, pmid=null, pmcid=null, year=2014, volume=41, issue=null, pageStart=433, pageEnd=442, url=null, language=null, rfNumber=[27], rfOrder=26, authorNames=Yaegashi J, Oakley BR, Wang CC, journalName=J Ind Microbiol Biot, refType=null, unstructuredReference= Yaegashi J , Oakley BR , Wang CC . Recent advances in genome mining of secondary metabolite biosynthetic gene clusters and the development of heterologous expression systems in Aspergillus nidulans[J]. J Ind Microbiol Biot, 2014, 41: 433-442., articleTitle=Recent advances in genome mining of secondary metabolite biosynthetic gene clusters and the development of heterologous expression systems in Aspergillus nidulans, refAbstract=null)], funds=[Fund(id=1220655374525453065, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, awardId=2018ZX09711001-008-001, language=CN, fundingSource=科技部“重大新药创制”科技重大专项(2018ZX09711001-008-001), fundOrder=null, country=null), Fund(id=1220655374617727757, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, awardId=2017-I2M-4-004, language=CN, fundingSource=中国医学科学院医学与健康科技创新工程(2017-I2M-4-004), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1220655369282572781, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369290961388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China), AuthorCompanyExt(id=1220655369299349997, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369282572781, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)]), AuthorCompany(id=1220655369433567730, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, xref=null, ext=[AuthorCompanyExt(id=1220655369437762034, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369433567730, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. School of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China), AuthorCompanyExt(id=1220655369446150644, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, companyId=1220655369433567730, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.沈阳药科大学中药学院, 辽宁 沈阳 110016)])], figs=[ArticleFig(id=1220655372759651017, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=HVGM6PWaGPnOsjgu1I4aog==, figureFileBig=3NIo3UzvxaJGYJf+CKdUyw==, tableContent=null), ArticleFig(id=1220655372856120013, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Figure 1, caption= Representative perylenequinone compounds and the compounds identified in this study (<strong>1</strong>-<strong>4</strong>) , figureFileSmall=HVGM6PWaGPnOsjgu1I4aog==, figureFileBig=3NIo3UzvxaJGYJf+CKdUyw==, tableContent=null), ArticleFig(id=1220655373044863701, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=e9lUSYn0YiDwyQ54JyjTDA==, figureFileBig=slZ1RspMBkHoBF1fMMxKCQ==, tableContent=null), ArticleFig(id=1220655373166498524, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Figure 2, caption= The plasmid maps , figureFileSmall=e9lUSYn0YiDwyQ54JyjTDA==, figureFileBig=slZ1RspMBkHoBF1fMMxKCQ==, tableContent=null), ArticleFig(id=1220655373292327649, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=4Q1y9xO5EuMDQ/ngs4vA6w==, figureFileBig=rL/BZLmc1hL8ozV2T8HR9A==, tableContent=null), ArticleFig(id=1220655373451711202, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Figure 3, caption= Comparative analysis of gene cluster <i>hpc</i> and <i>elc</i> , figureFileSmall=4Q1y9xO5EuMDQ/ngs4vA6w==, figureFileBig=rL/BZLmc1hL8ozV2T8HR9A==, tableContent=null), ArticleFig(id=1220655373560763109, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=yhAHWyVIqAvLHmRNyqE9TA==, figureFileBig=ucaJZf644XbF1qVTAr/Z6A==, tableContent=null), ArticleFig(id=1220655373720146666, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Figure 4, caption= The biosynthetic pathway speculation of hypocrellins with perylenequinone skeleton in <i>Shiraia bambusiccola</i> , figureFileSmall=yhAHWyVIqAvLHmRNyqE9TA==, figureFileBig=ucaJZf644XbF1qVTAr/Z6A==, tableContent=null), ArticleFig(id=1220655373845975791, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=dOR/sgiv2+Fi6AwwyP3pAg==, figureFileBig=a7dShYIJhGdxPNuOOgoyEQ==, tableContent=null), ArticleFig(id=1220655373942444787, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Figure 5, caption= A: The HPLC-MS analysis: heterologous expression combination <i>hpcA</i> (ⅰ), <i>hpcABCDF</i> (ⅱ-ⅲ), <i>Shiraia bambusiccola</i> extracting (ⅳ), Standard of hypocrellin A (HA) (ⅴ), Standard of hypocrellin B (HB) (ⅵ) and blank control group (ⅶ); B: UV chromatograms of products <strong>1</strong>-<strong>4</strong> , figureFileSmall=dOR/sgiv2+Fi6AwwyP3pAg==, figureFileBig=a7dShYIJhGdxPNuOOgoyEQ==, tableContent=null), ArticleFig(id=1220655374038913783, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Gene Primer sequences (5′ to 3′)
PKS-1-F CTGAGCTTCATCCCCAGCATCATTACACCTCAGCAATGGCGGAACCCATCAAGGTTTTC
PKS-1-R CAATGCGGTGGTATTGTCGAATTC
PKS-2-F GGTCCTTTTGATGCTGAAGAATTCG
PKS-2-R CCATTCATGACAAAACCTCCTAG
PKS-3-F TTGACGCTCTCTCTCAGCTAGGAG
PKS-3-R GTGGAGGACATACCCGTAATTTTCTGGGCATTTAAATTTAGGTGACAGCGAGTGGACTG
MTFAD-F TAACCATTACCCCGCCACATAGACACATCTAAACAATGGCTACGTTAACCTCCTTTAGC
MTFAD-R ACCAGTTCGGAAGATCAGGGTTTAAACGCGGCCGCGTGAGATTTGAGGTCGGCGAATTG
MT-F CCTGAGCTTCATCCCCAGCATCATTACACCTCAGCAATGTCTCTATTCCAACTCACTGC
MT-R AAAGGGTATCATCGAAAGGGAGTCATCCAATTTAAATAAGCAGCAGGAGAGTGGATAGG
FAD-F TTCTCTGAACAATAAACCCCACAGAAGGCATTTATGTTTGTCGAGAATTTACCCCAATG
FAD-R ATCAATTCACCGGAGTGGAAAGTCGATCACATGGGCTATG
LAC-F TAACCATTACCCCGCCACATAGACACATCTAAACAATGGCGTGTAATGTTTTCAAGGTC
LAC-R TGAGACCCAACAACCATGATACCAGGGGATTTAAATCCAAGAACACCAATAGAAAGTCG
glaA-F GCGGCCGCGTTTAAACCCTGATCTTCCGAACTGGTCGTAC
glaA-R TGCTGAGGTGTAATGATGCTGG
gpdA-F AGAAGCATACATAGCCCATGTGATCGACTTTCCACTCCGGTGAATTGATTTGGGTG
gpdA-R TGTTTAGATGTGTCTATGTGGCGG
), ArticleFig(id=1220655374139577082, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Table 1, caption=

Primers for PCR

, figureFileSmall=null, figureFileBig=null, tableContent=
Gene Primer sequences (5′ to 3′)
PKS-1-F CTGAGCTTCATCCCCAGCATCATTACACCTCAGCAATGGCGGAACCCATCAAGGTTTTC
PKS-1-R CAATGCGGTGGTATTGTCGAATTC
PKS-2-F GGTCCTTTTGATGCTGAAGAATTCG
PKS-2-R CCATTCATGACAAAACCTCCTAG
PKS-3-F TTGACGCTCTCTCTCAGCTAGGAG
PKS-3-R GTGGAGGACATACCCGTAATTTTCTGGGCATTTAAATTTAGGTGACAGCGAGTGGACTG
MTFAD-F TAACCATTACCCCGCCACATAGACACATCTAAACAATGGCTACGTTAACCTCCTTTAGC
MTFAD-R ACCAGTTCGGAAGATCAGGGTTTAAACGCGGCCGCGTGAGATTTGAGGTCGGCGAATTG
MT-F CCTGAGCTTCATCCCCAGCATCATTACACCTCAGCAATGTCTCTATTCCAACTCACTGC
MT-R AAAGGGTATCATCGAAAGGGAGTCATCCAATTTAAATAAGCAGCAGGAGAGTGGATAGG
FAD-F TTCTCTGAACAATAAACCCCACAGAAGGCATTTATGTTTGTCGAGAATTTACCCCAATG
FAD-R ATCAATTCACCGGAGTGGAAAGTCGATCACATGGGCTATG
LAC-F TAACCATTACCCCGCCACATAGACACATCTAAACAATGGCGTGTAATGTTTTCAAGGTC
LAC-R TGAGACCCAACAACCATGATACCAGGGGATTTAAATCCAAGAACACCAATAGAAAGTCG
glaA-F GCGGCCGCGTTTAAACCCTGATCTTCCGAACTGGTCGTAC
glaA-R TGCTGAGGTGTAATGATGCTGG
gpdA-F AGAAGCATACATAGCCCATGTGATCGACTTTCCACTCCGGTGAATTGATTTGGGTG
gpdA-R TGTTTAGATGTGTCTATGTGGCGG
), ArticleFig(id=1220655374277989117, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
No. 1 2
δH (J in Hz) δC δH (J in Hz) δC
1 134.1 131.3
1a 128.6 128.0
2 150.8 149.3
3 171.0 171.8
3a 107.0 106.8
3b 125.1 124.6
4 180.0 179.7
5 6.56, s 102.1 6.57, s 101.9
6 167.6 167.3
6a 117.9 117.6
7 167.6 167.8
7a 118.4 118.0
8 6.55, s 102.2 6.56, s 102.3
9 180.5 180.1
9a 106.9 107.2
9b 125.1 125.5
10 171.9 171.9
11 151.0 152.0
12 133.3 135.2
12a 127.8 128.4
13 3.51, d (12.2) 42.0 3.67, d (13.8) 42.6
2.63, d (12.2) 2.34, d (13.8)
14 78.9 78.7
15 3.44, s 60.9 3.72, s 64.4
16 207.5 206.7
17 1.89, s 30.2 1.83, s 28.6
18 1.70, s 27.1 1.78, s 24.9
2-OMe 4.11, s 61.8 4.27, s 61.1
6-OMe 4.07, s 56.6 4.08, s 56.6
7-OMe 4.07, s 56.7 4.07, s 56.7
11-OMe 4.11, s 62.2 4.18, s 62.0
4-OH 15.90, s 15.95, s
9-OH 15.95, s 16.06, s
14-OH 4.89, s 3.79, s
), ArticleFig(id=1220655374378652419, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1220655367277695328, language=CN, label=Table 2, caption=

1H (600 MHz) and 13C NMR (150 MHz) data of compounds 1 and 2 (CDCl3)

, figureFileSmall=null, figureFileBig=null, tableContent=
No. 1 2
δH (J in Hz) δC δH (J in Hz) δC
1 134.1 131.3
1a 128.6 128.0
2 150.8 149.3
3 171.0 171.8
3a 107.0 106.8
3b 125.1 124.6
4 180.0 179.7
5 6.56, s 102.1 6.57, s 101.9
6 167.6 167.3
6a 117.9 117.6
7 167.6 167.8
7a 118.4 118.0
8 6.55, s 102.2 6.56, s 102.3
9 180.5 180.1
9a 106.9 107.2
9b 125.1 125.5
10 171.9 171.9
11 151.0 152.0
12 133.3 135.2
12a 127.8 128.4
13 3.51, d (12.2) 42.0 3.67, d (13.8) 42.6
2.63, d (12.2) 2.34, d (13.8)
14 78.9 78.7
15 3.44, s 60.9 3.72, s 64.4
16 207.5 206.7
17 1.89, s 30.2 1.83, s 28.6
18 1.70, s 27.1 1.78, s 24.9
2-OMe 4.11, s 61.8 4.27, s 61.1
6-OMe 4.07, s 56.6 4.08, s 56.6
7-OMe 4.07, s 56.7 4.07, s 56.7
11-OMe 4.11, s 62.2 4.18, s 62.0
4-OH 15.90, s 15.95, s
9-OH 15.95, s 16.06, s
14-OH 4.89, s 3.79, s
)], attaches=null, journal=Journal(id=1189982048455397383, delFlag=0, nameCn=药学学报, nameEn=Acta Pharmaceutica Sinica, nameHistory1=null, nameHistory2=null, issn=0513-4870, eissn=null, cn=11-2163/R, coden=null, periodic=0, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=BTxjudbJDVO4PqdBR6On6Q==, journalPrice=null, startedYear=null, abbrevIsoEn=null, journalRemark=null, publicationField=null, createdTime=1761643429151, updatedTime=1761735768113, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=A, firstLetterEn=A, subjectCode=Life Sciences, subjectName=Life Sciences, subjectCodeEn=Life Sciences, subjectNameEn=null, picCn=BTxjudbJDVO4PqdBR6On6Q==, picEn=c4l1ckL55nWbhl1KrFdWIA==, jcr=null, cjcr=null, exts=[JournalExt(id=1190369346338783397, language=CN, name=药学学报, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1761735768160, updatedTime=1761735768160, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://www.yxxb.com.cn/journalx_yxxb/authorLogOn.action, submissionEditorUrl=https://www.yxxb.com.cn/journalx_yxxb/editorLogOn.action, submissionReviewUrl=https://www.yxxb.com.cn/journalx_yxxb/expertLogOn.action, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1190369346376532134, language=EN, name=Acta Pharmaceutica Sinica, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1761735768169, updatedTime=1761735768169, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://www.yxxb.com.cn/journalx_yxxb/authorLogOn.action, submissionEditorUrl=https://www.yxxb.com.cn/journalx_yxxb/editorLogOn.action, submissionReviewUrl=https://www.yxxb.com.cn/journalx_yxxb/expertLogOn.action, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1189982191388893191, websiteList=[Website(id=1189982271588340489, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1189982191388893191, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/yxxb/CN, language=CN, createTime=1761643482348, createBy=18614031015, updateTime=1761643498101, updateBy=18614031015, name=药学学报-中文, tplId=1146099689490845704, title=药学学报, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1189982873114448678, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=articleTextType, value=kx, createTime=1761643625763, updateTime=1761643625763, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873093477155, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=banner, value=null, createTime=1761643625758, updateTime=1761643625758, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873135420201, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=grayFlag, value=0, createTime=1761643625768, updateTime=1761643625768, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873085088546, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=logo, value=https://castjournals.cast.org.cn/joweb/yxxb/CN/file/pic?fileId=w+t2v8bJnX5lh3+hRRJcDA==, createTime=1761643625756, updateTime=1761643625756, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873152197419, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=minRunFlag, value=0, createTime=1761643625772, updateTime=1761643625772, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873110254373, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/yxxb/CN/file/pic, createTime=1761643625762, updateTime=1761643625762, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873143808810, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=silenceFlag, value=0, createTime=1761643625770, updateTime=1761643625770, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873101865764, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1761643625760, updateTime=1761643625760, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873122837287, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=themeColor, value=null, createTime=1761643625765, updateTime=1761643625765, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873127031592, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=themeStyle, value=null, createTime=1761643625766, updateTime=1761643625766, creator=18614031015, updator=18614031015)]), Website(id=1189982271655449355, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1189982191388893191, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/yxxb/EN, language=EN, createTime=1761643482364, createBy=18614031015, updateTime=1761643514085, updateBy=18614031015, name=药学学报-英文, tplId=1146101810881728533, title=Acta Pharmaceutica Sinica, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1189982903015633534, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=articleTextType, value=kx, createTime=1761643632892, updateTime=1761643632892, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982902990467707, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=banner, value=null, createTime=1761643632886, updateTime=1761643632886, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903036605057, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=grayFlag, value=0, createTime=1761643632897, updateTime=1761643632897, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982902982079098, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=logo, value=https://castjournals.cast.org.cn/joweb/yxxb/EN/file/pic?fileId=w+t2v8bJnX5lh3+hRRJcDA==, createTime=1761643632884, updateTime=1761643632884, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903053382275, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=minRunFlag, value=0, createTime=1761643632901, updateTime=1761643632901, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903007244925, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/yxxb/EN/file/pic, createTime=1761643632890, updateTime=1761643632890, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903044993666, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=silenceFlag, value=0, createTime=1761643632899, updateTime=1761643632899, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982902998856316, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1761643632888, updateTime=1761643632888, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903019827839, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=themeColor, value=null, createTime=1761643632893, updateTime=1761643632893, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903028216448, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=themeStyle, value=null, createTime=1761643632895, updateTime=1761643632895, creator=18614031015, updator=18614031015)])], journalTitle=药学学报, weixinUrl=null, journalUrl=https://www.yxxb.com.cn/aps, iacademicId=null, status=1, seqNo=null, journalTitleEn=Acta Pharmaceutica Sinica, journalPhotoCn=BTxjudbJDVO4PqdBR6On6Q==, journalPhotoEn=c4l1ckL55nWbhl1KrFdWIA==, journalFirstLetter=A, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false), detailUrlCn=https://castjournals.cast.org.cn/joweb/yxxb/CN/10.16438/j.0513-4870.2020-0698, detailUrlEn=https://castjournals.cast.org.cn/joweb/yxxb/EN/10.16438/j.0513-4870.2020-0698, pdfUrlCn=https://castjournals.cast.org.cn/joweb/yxxb/CN/PDF/10.16438/j.0513-4870.2020-0698, pdfUrlEn=https://castjournals.cast.org.cn/joweb/yxxb/EN/PDF/10.16438/j.0513-4870.2020-0698, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
药用真菌竹黄主要活性成分的异源生物合成
收藏切换
PDF下载
张亚龙 1, # , 张乐 1, # , 高洁 1 , 柏健 1 , 闫道江 1 , 张元元 2 , 胡友财 1, *
药学学报 | 研究论文 2020,55(7): 1691-1698
收起
收藏切换
药学学报 | 研究论文 2020, 55(7): 1691-1698
药用真菌竹黄主要活性成分的异源生物合成
全屏
张亚龙1, #, 张乐1, #, 高洁1, 柏健1, 闫道江1, 张元元2, 胡友财1, *
作者信息
  • 1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050
  • 2.沈阳药科大学中药学院, 辽宁 沈阳 110016

通讯作者:

*胡友财, E-mail:
Hetero-biosynthesis of the main bioactive components from medicinal fungus Shiraia bambusiccola
Ya-long ZHANG1, Le ZHANG1, Jie GAO1, Jian BAI1, Dao-jiang YAN1, Yuan-yuan ZHANG2, You-cai HU1, *
Affiliations
  • 1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 2. School of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
出版时间: 2020-07-12 doi: 10.16438/j.0513-4870.2020-0698
文章导航
收藏切换
摘要
收起

竹黄是我国一种重要的药用真菌资源，其主要活性成分竹红菌素类化合物已作为天然光敏剂广泛应用于食品、医药、农药等领域，其中竹红菌素软膏已用于临床。然而作为一种珍稀易危的物种，野生竹黄的资源非常有限。而竹红菌素结构复杂化学合成成本高，因此亟待一种有效的方法在保护竹黄野生资源的同时合理利用其药用价值。本文即采用合成生物学技术来获取竹黄中的主要活性成分，以期摆脱对野生资源的依赖。通过对竹黄菌Shiraia sp.cfcc 84681的全基因组进行细致的生物信息学分析，从中挖掘到一条竹红菌素生物合成的候选基因簇hpc；并成功构建了该基因簇的异源表达系统，获得一株产竹红菌素类化合物的重组菌株。该菌株主要产竹红菌甲素和异竹红菌甲素，这与野生竹黄提取物的主要成分基本一致。本研究有望为解决野生竹黄的资源短缺问题提供一种新的有效途径。

药用真菌  /  竹黄  /  竹红菌素  /  异源生物合成  /  合成生物学

Shiraia bambusiccola is an important medicinal fungus in China. Hypocrellins with perylenequinone skeleton are main bioactive components of Shiraia bambusiccola, which are widely used in food, medicine, pesticide and other fields as natural photosensitizers. For example, "hypocrellin ointment" has already been used clinically. As a rare and vulnerable species, wild Shiraia bambusiccola resources are very limited. Due to the complex structure and chanllenge in chemical total synthesis of hypocrellins, it is urgent to find an effective strategy to rationally utilize its medicinal value while protecting the wild resources. In this study, a candidate gene cluster hpc was identified in Shiraia sp. cfcc 84681 based on careful bioinformatic analysis. A heterologous expression system for hpc gene cluster was successfully constructed and a mutant strain with high yield of hypocrellins was obtained, which mainly produced hypocrellin A and isohypocrellin A. The main ingredients in the mutant strain are consistent with that in the wild Shiraia bambusiccola. These results provide a new strategy to solve the shortage of wild Shiraia bambusiccola resources.

medicinal fungus  /  Shiraia bambusiccola  /  hypocrellin  /  hetero-biosynthesis  /  synthetic biology
张亚龙, 张乐, 高洁, 柏健, 闫道江, 张元元, 胡友财. 药用真菌竹黄主要活性成分的异源生物合成. 药学学报, 2020 , 55 (7) : 1691 -1698 . DOI: 10.16438/j.0513-4870.2020-0698
Ya-long ZHANG, Le ZHANG, Jie GAO, Jian BAI, Dao-jiang YAN, Yuan-yuan ZHANG, You-cai HU. Hetero-biosynthesis of the main bioactive components from medicinal fungus Shiraia bambusiccola[J]. Acta Pharmaceutica Sinica, 2020 , 55 (7) : 1691 -1698 . DOI: 10.16438/j.0513-4870.2020-0698
正文
收起
药用真菌竹黄是我国一种重要的中药资源, 为肉座科真菌Shiraia bambusicola的子座。竹黄具有化痰止咳、活血祛风、补中益气的功效[1]。据《本草纲目》记载, 竹黄可用于治疗小儿惊风等症。此外竹黄民间常用于治疗气管炎、百日咳、跌打损伤、坐骨神经痛等[2], 亦可浸泡于黄酒或米酒中用于治疗关节炎。鉴于竹黄的广泛功能, 每到竹黄采摘季节都有很多客商贩卖竹黄。竹黄菌是一种寄生真菌, 需寄生在刚竹属、短穗竹属的竹竿上, 其多生长在将衰败或已衰败的竹林中, 并受季节、地域环境、寄主等多种因素的严格限制[3]。竹黄菌在阴凉潮湿的环境中产量较高, 干燥向阳环境则产率极低, 并且每年三月开始萌发, 五六月份才开始成熟, 采摘周期短, 加之环境的逐年恶化, 这些都导致了竹黄的野生资源非常有限, 极大地限制了竹黄资源的开发利用[4]。在生态环境部和中国科学院发布的《中国生物多样性红色名录—大型真菌卷》中, 竹黄已被认定为易危物种。易危类物种代表在过去10年或三世代内该物种减少比例大于50%。如果野生竹黄资源长期被过度开采并得不到有效的保护, 这类资源有可能濒临灭绝。竹黄之所以被广泛应用得益于其显著的药用价值, 现代药理学表明竹红菌素是竹黄的主要活性成分, 是一类最早发现于竹红菌子座中的多种苝醌类衍生物的混合物, 也是我国最早发现的一种新型优良光敏剂, 广泛应用于临床治疗胃病、风湿性关节炎和皮肤病[5-7]。此外, 该类化合物在光照时表现出抗肿瘤、抗病毒、抗微生物等活性[8, 9]。目前竹红菌素软膏等已作为药品临床用于治疗外阴白色病变、外阴瘙痒等。竹红菌素主要包括竹红菌甲素(hypocrellin A, HA)、竹红菌乙素(hypocrellin B, HB)、痂囊腔菌素A (elsinochrome A)和尾孢菌素(cercosporin)等(图 1)[10, 11]。鉴于该类苝醌类化合物的重要价值, 国内外研究者对其产量优化、分离纯化、化学合成等领域进行了多项研究。竹红菌素类化合物的获取单纯依靠传统的提取分离受到野生资源的极大限制, 而采用化学合成的方法对竹红菌甲素进行全合成需要19步, 产率仅为1.6%[12-14]。合成生物学的快速发展已在医药、能源等诸多领域取得举世瞩目成果, 如抗疟药物青蒿素的生物合成等[15, 16]。合成生物学有望成为有效保护和合理利用珍稀濒危野生药用资源的现代化途径。江南大学的研究学者对竹黄菌中竹红菌素的形成进行了研究, 阐明了竹黄抵御外界环境的抗氧化系统, 建立了玉米糁固态发酵法产竹红菌素的方法并对发酵条件进行了优化和放大以提高竹红菌素的产量, 但这离工业化生产仍然存在差距[17-20]。随着大量真菌基因组测序的完成, 来自于烟草尾孢菌(Cercospora nicotiae)的ctb基因簇、竹黄菌(Shiraia sp. strain Slf14)的hyp基因簇、小麦病原菌(wheat pathogen Parastagonospora nodorum)的elc基因簇被推测可能参与不同类型的苝醌类化合物的生物合成[21-24]。其中, 澳大利亚学者Chooi通过丝状真菌异源表达体系证实了来源于小麦病原菌的elc基因簇中聚酮合酶PKS、具有甲基转移酶和FAD依赖氧化酶活性的双功能蛋白MT-FAD、甲基转移酶MT、漆酶Laccase、FAD依赖的氧化酶、黄素依赖的单加氧酶FMO等共同催化痂囊腔菌素A (elsinochrome A)等的生物合成[25]。这些研究为采用合成生物学技术解决野生竹黄资源短缺问题奠定了基础。为获得高产竹红菌素类化合物的重组菌株, 本研究从竹黄菌Shiraia sp. cfcc 84681 (该菌株在实验室发酵条件下未产竹红菌素类化合物)中挖掘到一个可能产竹红菌素及其类似物的候选基因簇hpc, 成功构建了hpc基因簇异源表达系统, 并获得一株该类化合物的高产重组菌株, 所得产物的成分与野生竹黄提取物主要成分基本一致。本项研究不但为保护竹黄野生资源奠定基础, 也为通过合成生物学技术有效保护和合理利用珍稀野生药用资源提供借鉴模式。
材料与方法
收起
菌株、培养基等实验材料和培养条件  竹黄菌Shiraia sp. cfcc 84681来源于中国林业微生物菌种保藏管理中心。全基因组测序由北京诺禾致源科技股份有限公司完成。竹黄菌采用土豆培养基(PDA)在28 ℃进行培养用以传代, 并用于提取基因组DNA。构巢曲霉(Aspergillus nidulans)菌株用于异源表达操作, 使用产孢培养基(CD培养基)在37 ℃进行培养用以传代; 用于异源表达的突变株换用发酵培养基(CD-ST培养基, CD培养基中的葡萄糖被淀粉替代)进行发酵(28 ℃)。酵母菌株Y31用于重组质粒的构建, 在30 ℃条件下接种到相应缺陷的培养基(SD-Ura minus)。Escherichia coli DH10B用于常规的基因克隆; 大肠杆菌均用常规LB、SOC培养基培养, 培养温度为37 ℃, 根据需要加入100 μg·mL-1氨苄青霉素对菌株进行抗性筛选。用于原生质体制备的缓冲液有Osmotic缓冲液、trapping缓冲液和STC培养基。Osmotic缓冲液配方: 1.2 mol·L-1 MgSO4, 10 mmol·L-1磷酸盐缓冲液, pH调到5.8。Trapping缓冲液配方: 0.6 mol·L-1 Sorbitol, 0.1 mol·L-1 Tris-HCl, pH 7.0。STC缓冲液配方: 1.2 mol·L-1 Sorbitol, 10 mmol·L-1 CaC12, 10 mmol·L-1 Tris-HCl, pH 7.5。以上缓冲液均需过滤除菌并在4 ℃条件下保存。野生竹黄药材购自安国药材市场。
引物  本文所用的PCR扩增引物见表 1。
主要试剂  高保真DNA聚合酶Q5 High-Fidelity DNA Polymerase、限制性内切酶购自美国New England Biolabs公司, 酵母质粒提取试剂盒Zymoprep Yeast Plasmid Miniprep Kit来自美国Zymo Research生物科技公司, DNA回收试剂盒和质粒提取试剂盒均来自Axygen公司; 裂解酶lysig酶和yatalase酶分别购自Sigma公司和Takara公司; 色谱甲醇、色谱乙腈购自美国Fisher公司; 分析色谱柱(ACQUITY UPLC® BEH, 1.7 µm, 2.1 mm×50 mm, C18 column)来自美国Waters公司; Silgreen ODS半制备色谱柱(250 mm×10 mm, 5 μm)购自北京绿百草科技发展有限公司。实验室所用的各种引物由南京金斯瑞生物科技公司合成, DNA测序由北京六合华大基因科技有限公司完成。
DNA基本操作  分子生物学常规操作参照分子克隆实验指南。
三元穿梭质粒的构建  利用酵母重组的策略构建glaA、gpdA、amyB不同强启动子启动的三元穿梭质粒, 将母核基因hpcA构建在含有glaA启动子的PANU载体上, 即质粒PANU-hpcA(PKS); 构建过程如下:以基因组DNA为模板, 用设计的带有至少30 bp重叠区的3对引物PKS-1-F/PKS-1-R、PKS-2-F/PKS-2-R、PKS-3-F/PKS-3-R分3段扩增hpcA目的片段, 将这3段片段和用限制性内切酶NotI酶切线性化的PANU载体在酵母感受中重组, 将筛选到的酵母阳性转化子转到大肠杆菌超级感受态。筛选阳性转化子并提取质粒。按照上述方法将基因hpcB和hpcC构建在载体PANR上, 构建过程如下:分别用3对引物MTFAD-F/MTFAD-R、glaA-F/glaA-R和MT-F/MT-R扩增hpcB和hpcC和启动子glaA, 将这3段片段和用限制性内切酶BamHI线性化载体PANR (带有gpdA启动子)在酵母感受态中重组。按照上述方法构建质粒PANP-hpcD(FAD)-hpcF(Lac), 将用3对引物FAD-F/FAD-R、LAC-F/LAC-R和gpdA-F/gpdA-R扩增得到的基因片段hpcD、hpcF、启动子gpdA和BamHI酶切线性化的载体PANP (带有AmyB启动子)在酵母细胞中重组。将以上得到的3个质粒PANU-hpcA(PKS)、PANR-hpcB(MTFAD)-hpcC(MT)和PANP-hpcD(FAD)-hpcF(Lac)的阳性转化子送测序验证。3个质粒的质粒图谱如图 2所示。
相关菌株的发酵与代谢产物的分析  将以下质粒组合导入模式真菌构巢曲霉中, 获得包含不同基因组合的构巢曲霉异源表达菌株。相应组合如下所示:重组菌株hpcA:包含单独的聚酮合酶基因的质粒PANU-hpcA(PKS); 重组菌株hpcABCDF:包含质粒PANU-hpcA(PKS)、PANR-hpcB(MTFAD)-hpcC(MT)和PANP-hpcD(FAD)-hpcF(Lac)。利用相应的营养缺陷型培养基uracil (pyrG), pyridoxine (pyroA)和riboflavin (riboB)筛选阳性转化子, 即得到异源表达菌株。此外, 将空质粒PANU、PANR、PANP转入构巢曲霉宿主细胞中, 作为空白对照组。
将不同组合的阳性转化子接种到固体发酵培养基CD-ST中, 28 ℃条件下培养5天然后用乙酸乙酯萃取。乙酸乙酯层离心浓缩后用100 μL甲醇复溶, 13 000 r·min-1离心10 min, 取上清液经0.22 μm滤膜过滤, 滤液用于超高效液相色谱-串联单四极杆质谱(UPLC-MS)检测。液质联用仪为Waters ACQUITY UPLC H-Class超高效液相色谱-QDa质谱(美国Waters公司)。流动相A相为乙腈(v/v, 0.02%甲酸), B相为0.02% (v/v)甲酸水溶液。采用梯度洗脱的方法, 即A相在8 min内由5% (v/v)线性递增至99% (v/v), 流速为0.4 mL·min-1, 柱温25 ℃, 检测波长为200~800 nm。色谱柱为ACQUITY UPLC® BEH, 1.7 µm, 2.1 mm×50 mm, C18柱, 检测器为光电二极管阵列检测器(PDA)和单四极杆质谱检测器(QDa)。质谱检测条件:采用电喷雾离子源, 正负离子交替扫描模式, 探针温度: 600 ℃, 源温度: 120 ℃, 毛细管电压: 0.8 kV, 锥孔电压: 15 V, 采样速率:每秒10点。发酵产物的NMR谱由中国医学科学院药物研究所分析测试中心完成(Bruker AVIII-600核磁共振检测仪)。圆二色谱(甲醇溶解)使用JASCO 815圆二色谱仪测定。
中药竹黄及异源表达发酵产物的提取与检测  取干燥竹黄药材50 g, 将其碎成粉末, 加入甲醇超声提取3次, 合并提取液并浓缩; 取适量竹黄药材提取物溶于200 μL甲醇中, 然后经13 000 r·min-1离心10 min。上清液经0.22 μm滤膜过滤后用于UPLC-MS检测, 检测条件同异源表达产物检测条件。
将重组菌株A. nidulans (hpcA)的孢子接种到1 L固体CD-ST培养基上, 在28 ℃条件下培养9天。经乙酸乙酯超声提取3次, 得粗提物500 mg。粗提物经中压(洗脱条件为20%乙腈-水梯度升至100%乙腈)富集后, 再经半制备纯化(流动性条件为含0.06%甲酸的60%甲醇-水)得到化合物4 (5 mg)。将重组菌株A. nidulans (hpcABCDF)的孢子接种到4 L固体CD-ST培养基上, 在28 ℃条件下培养8天。经乙酸乙酯超声提取3次, 得粗提物4 g。粗提物经中压(洗脱条件为20%乙腈-水梯度升至100%乙腈)富集后, 得到含目标产物的粗样品Ⅰ (45 mg)和粗样品Ⅱ (40 mg)。粗样品Ⅰ和Ⅱ分别再经半制备液相色谱纯化(流动性条件均为56%乙腈-水), 分别得到化合物2 (7 mg)和化合物1 (6.8 mg)。
结果与讨论
收起
1 竹红菌素类生物合成基因簇分析及合成途径推测
为寻找野生竹黄的可替代资源, 积累高产竹红菌素类化合物菌株的基因资源, 从一株竹黄菌Shiraia sp. cfcc 84681的全基因组中挖掘到一个可能产竹红菌素类苝醌类化合物的基因簇hpc。如图 3所示, 该基因簇分布在两个Scaffold中, 它们之间用黑色虚线区分。采用生物信息学的方法对该基因簇进行分析, 发现该基因簇与elc基因簇高度相似, 包括可编码竹红菌素类化合物生物合成所需的5个关键酶, 即聚酮合酶HpcA(PKS)、兼具甲基转移酶和FAD依懒性单加氧酶双结构域的双功能酶HpcB (MTFAD)、甲基转移酶HpcC(MT)、FAD依懒性氧化还原酶HpcD (FAD)和漆酶HpcF (Lac), 说明hpc基因簇可能负责该类化合物的生物合成。此外, 该基因簇还包含黄素单加氧酶HpcE (FMO)、短链脱氢/还原酶HpcG (SDR)、未知功能蛋白HpcH和锌指转录因子HpcI (zinc-finger transcription factor)。
根据竹红菌素类化合物的结构特点以及上述基因簇组成, 推测其生物合成途径如图 4:在聚酮合酶HpcA作用下合成单体化合物ⅰ, 之后在双功能酶HpcB作用下发生甲基化和开环, 然后在甲基转移酶HpcC作用下生成中间体ⅱ; 在FAD依懒性氧化酶HpcD和漆酶HpcF共同作用下, ⅱ发生二聚化, 并经自发的羟醛缩合生成竹红菌素类化合物。根据上述推测, 可以先异源表达聚酮合酶HpcA来验证该基因簇。而为了实现最终竹红菌素类化合物的生成, 可以同时异源表达HpcABCDF。
2 异源表达产物的检测与鉴定
2.1 UPLC-MS结果分析
对重组菌株A. nidulans (hpcA)和重组菌株A. nidulans (hpcABCDF)的发酵产物、空白对照(未导入异源基因的构巢曲霉的发酵产物)、野生竹黄提取物分别进行UPLC-MS检测(图 5A)。与空白对照(图 5A-ⅶ)相比, 重组菌株A. nidulans (hpcA)的发酵产物(图 5A-ⅰ)中明显出现一个新的色谱峰4 (tR = 4.46 min), 提示其为聚酮合酶HpcA催化形成的聚酮类产物。质谱显示4的准分子离子峰为m/z 259 [M+H]+, 其UV吸收峰如图 5B所示, 这与该类聚酮合酶催化合成的产物nor-toralactone一致。化合物4的鉴定也证明候选基因簇hpc是负责竹红菌素类化合物的生物合成。
而重组菌株A. nidulans (hpcABCDF)的发酵产物(图 5A-ⅱ)比空白对照组多出两个明显的色谱峰(1, tR = 5.92 min; 2, tR = 5.75 min)以及一个微小的色谱峰(3, tR = 6.21 min), 其中色谱峰1的保留时间、相对分子质量和紫外吸收与标准品竹红菌甲素(HA, 图 5A-v)一致, 推测该化合物为竹红菌甲素; 而色谱峰2的相对分子质量为546, 紫外吸收与1类似, 提示其也是竹红菌素类化合物, 其结构之后得到分离鉴定。此外, 色谱峰3的保留时间、相对分子质量和紫外吸收与标准品竹红菌乙素(HB, 图 5A-ⅵ)完全一致, 可以鉴定为竹红菌乙素(因含量过低, 后续未分离)。对比分析重组菌株A. nidulans (hpcABCDF)的发酵产物(图 5A-ⅱ)和野生竹黄提取物色谱图(图 5A-ⅳ)可以发现两者的成分基本一致, 均含主成分1、2以及微量成分3, 仅仅在相对含量上略有差别。其中, 重组菌株中HB (3)的含量低于野生竹黄提取物中的量, 推测可能是因碱性或者加热条件会促进HA自发脱水生成HB, 而野生竹黄生长时间长导致较多HA转化为HB, 因此野生竹黄药材中HB的含量要高于重组菌株。
2.2 异源表达产物的结构鉴定
化合物4为淡黄色粉末, ESIMS显示其准分子离子峰m/z 259 [M+H]+。其1H NMR (600 MHz, DMSO-d6)谱呈现1个羟基氢信号[δH 10.25 (s, 1H)]、3个芳香氢信号[δH 6.96 (1H, s), 6.56 (1H, s), 6.42 (1H, s)]、1个烯氢信号[δH 6.29 (1H, s)]以及1个单峰甲基信号[δH 2.20 (3H, s)]。经与文献中的NMR数据对比, 化合物4鉴定为已知化合物nor-toralactone[25]。
化合物1为深红色固体, ESI-MS显示其准分子离子峰m/z 547 [M+H]+。其核磁数据如表 2所示, 在1H NMR谱中显示4个甲氧基氢信号[δH 4.11 (6H, s), 4.07 (6H, s)], 同时在碳谱中显示21个化学位移值大于100.0的低场碳信号, 结合其特征性的紫外吸收, 提示其为竹红菌素类化合物。对比该化合物的NMR数据与已知化合物竹红菌甲素(hypocrellin A)的NMR数据, 两者完全一致, 并且它们的圆二色谱(CD)的Cotton效应[533 nm (-7.1), 477 nm (+3.0)]也一致[26], 表明化合物1的平面结构和立体构型与竹红菌甲素均一致。化合物2同样为深红色固体, ESI-MS显示其与1拥有相同的分子量。该化合物的NMR数据和CD数据[582 nm (-0.9), 542 nm (-0.4), 469 nm (+3.7), 352 nm (-4.2)]与文献报道的已知化合物一致[22], 其与竹红菌甲素的结构差别在于C14、C15位的构型不同。本文将其命名为异竹红菌甲素(isohypocrellin A)。
3 小结
本文对一株竹黄菌Shiraia sp进行了全基因组测序, 并结合生物信息学分析从其全基因中筛选到一条可能产竹红菌素类化合物的基因簇hpc, 该基因簇包含参与竹红菌素类化合物生物合成的5个基因hpcA、hpcB、hpcC、hpcD和hpcF。此外, 该基因簇中的hpcE和hpcG也尝试异源表达实验证实二者均不直接参与HA类化合物的生物合成, 因此在本文实验部分并未提及。本文采用构巢曲霉表达系统成功构建了hpc基因簇的高效表达菌株, 获得了竹红菌甲素(1)和异竹红菌甲素(2), 产量分别为1.7和1.8 mg·L-1 (以实际分离得到的纯化合物量计), 说明该基因簇有进一步优化开发成工业发酵菌株的潜力。
讨论
收起
药用资源的保障供应是中药与天然药物可持续发展的基础。据统计, 我国有大量具有药用价值的物种分别处于近危、易危、濒危、极危甚至灭绝状态。如何有效保护并合理利用这些珍贵的野生药用资源是中药、天然药物研究领域亟待解决的问题。异源生物合成作为合成生物学的重要技术之一是不依赖于野生药用资源而绿色获取天然药物活性成分的有效途径。与野生资源有限相比, 异源生物合成所需的基因资源可通过克隆重复获取, 因此有望摆脱对野生资源的依赖。
本研究以易危物种竹黄作为切入点, 充分利用该物种的基因组资源, 通过在构巢曲霉中表达目标化合物的生物合成基因, 实现目标化合物的异源生物合成, 从而获取竹黄的主要活性成分。构巢曲霉异源表达系统与大肠杆菌、酵母表达系统等相比在表达真核生物来源的基因方面具有明显优势, 该系统在克隆基因簇时不需要去除内含子, 操作简便, 并且采用在每个表达的目的基因前加入强启动子的方式有利于目标化合物的大量积累[27], 因此构巢曲霉也非常适合于药用真菌中活性成分异源表达的底盘。利用该系统成功构建了竹红菌素类化合物的重组菌株, 并且该菌株产生的主要成分竹红菌甲素和异竹红菌甲素以及微量竹红菌乙素, 与野生竹黄的主要活性成分刚好一致。同时该重组菌株遗传操作稳定且培养周期短, 成本低廉且易于操作。因此, 该菌株有开发成商业菌株的潜力, 也为寻找药用竹黄资源的替代方法提供了可能性。如果结合启动子优化、培养条件、培养基种类优化等方法, 有望进一步提高竹红菌素类化合物的产量。总之, 本研究不但为解决药用真菌竹黄野生资源短缺的问题打下坚实基础, 也为利用合成生物学技术来绿色获取微量、珍稀天然药物的活性物质提供可借鉴的途径。
作者贡献:张亚龙和张乐作为共同第一作者, 分别负责实验设计、基因簇异源表达菌株的构建和发酵产物的提取分离, 以及质粒的构建和稿件撰写。高洁、柏健、闫道江、张元元分别负责文献的调研及整理, 核磁谱图分析、构巢曲霉异源表达系统的优化以及野生竹黄药材的提取; 胡友财作为通讯作者全面负责实验设计, 稿件撰写与修改等。
利益冲突:本文的研究内容无任何利益冲突。
基金
收起
  • 科技部“重大新药创制”科技重大专项(2018ZX09711001-008-001)
  • 中国医学科学院医学与健康科技创新工程(2017-I2M-4-004)
文献
收起
参考文献 引证文献
排序方式：
[1]
Liang XH , Cai YJ , Liao XR et al . The progress of research on medicinal fungus Shiraia bambusicola[J]. J Food Sci Biotechnol (食品与生物技术学报), 2008, 27: 21-26. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=wxqgdxxb200805004
[2]
Zhong SR , Zhao H , Li AM et al . Potential TCM-Shiraia bambusicola[J]. Chin Tradit Herb Drugs (中草药), 2002, 33: 372-374. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zcy200204041
[3]
Lai GH , Fu LY . Study on the main host plants of Shiraia bambusicola[J]. Chin Wild Plant Resour (中国野生植物资源), 2000, 19: 8-11.
[4]
Jia XM , Xu XH , Zhuang BC et al . The progress of biological reasearch of medicinal fungus Shirar bambusicola[J]. Microbiol China (微生物学通报), 2006, 33: 147-150.
[5]
Cui LQ . Investigate the clinical value of bamboo mushroom ointment in the treatment of leukoplakia[J]. China Health Standard Manag (中国卫生标准管理), 2017, 8: 108-109. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgwsbzgl201720057
[6]
Zhenjun D , Lown JW . Hypocrellins and their use in photosensitization[J]. Photochem Photobiol, 1990, 52: 609-616.
[7]
Weiss U , Merlini L , Nasini G . Naturally occurring perylenequinones[J]. Fortschr Chem Org Naturst, 1987, 52: 1-71. https://link.springer.com/chapter/10.1007%2F978-3-7091-8906-1_1
[8]
Chaloupka R , Sureau F , Kocisova E et al . Hypocrellin A photosensitization involves an intracellular pH decrease in 3T3 cells[J]. Photochem Photobiol, 1998, 68: 44-50.
[9]
Guo LY , Yan SZ , Tao X et al . Evaluation of hypocrellin a-loaded lipase sensitive polymer micelles for intervening methicillin-resistant Staphylococcus aureus antibiotic-resistant bacterial infection[J]. Mater Sci Eng C Mater Biol Appl, 2020, 106: 110230-110241.
[10]
Kishi T , Tahara S , Taniguchi N et al . New perylenequinones from Shiraia bambusicola[J]. Planta Med, 1991, 57: 376-379.
[11]
Mulrooey CA , O'Brien EM , Morgan BJ et al . Perylenequinones:isolation, synthesis, and biological activity[J]. Eur J Org Chem, 2012, 21: 3887-3904. https://pubmed.ncbi.nlm.nih.gov/24039544/
[12]
O'Brien EM , Morgan BJ , Kozlowski MC . Dynamic stereochemistry transfer in a transannular aldol reaction:total synthesis of hypocrellin A[J]. Angew Chem Int Ed, 2008, 47: 6877-6880.
[13]
O'Brien EM , Morgan BJ , Mulrooney CA et al . Perylenequinone natural products:total synthesis of hypocrellin A[J]. J Org Chem, 2010, 75: 57-68.
[14]
Morgan BJ , Dey S , Johnson SW et al . Design, synthesis, and investigation of protein kinase C inhibitors:total syntheses of (+)-calphostin D, (+)-phleichrome, cercosporin, and new photoactive perylenequinones[J]. J Am Chem Soc, 2009, 131: 9413-9425.
[15]
Dymond JS , Richardson SM , Coombes CE et al . Synthetic chromosome arms function in yeast and generate phenotypic diversity by design[J]. Nature, 2011, 477: 471-476.
[16]
Paddon CJ , Westfall PJ , Pitera DJ et al . High-level semi-synthetic production of the potent antimalarial artemisinin[J]. Nature, 2013, 496: 528-532.
[17]
Gao RJ , Xu ZC , Deng HX et al . Enhanced hypocrellin production of Shiraia sp. SUPER-H168 by overexpression of alpha-amylase gene[J]. PLoS One, 2018, 13: e0196519.
[18]
Gao RJ , Deng HX , Guan ZB et al . Enhanced hypocrellin production via coexpression of alpha-amylase and hemoglobin genes in Shiraia Bambusicola[J]. AMB Express, 2018, 8: 71-81.
[19]
Cai YJ , Liang XH , Liao XR et al . High-yield hypocrellin A production in solid-state fermentation by Shiraia sp. SUPER-H168[J]. Appl Biochem Biotechnol, 2010, 160: 2275-2286.
[20]
Gao RJ , Xu ZC , Deng HX et al . Influences of light on growth, reproduction and hypocrellin production by Shiraia sp. SUPER-H168[J]. Arch Microbiol, 2018, 200: 1217-1225.
[21]
Chen HQ , Lee MH , Chung KR . Functional characterization of three genes encoding putative oxidoreductases required for cercosporin toxin biosynthesis in the fungus Cercospora nicotianae[J]. Microbiology, 2007, 153: 2781-2790.
[22]
Newman AG , Townsend CA . Molecular characterization of the cercosporin biosynthetic pathway in the fungal plant pathogen Cercospora nicotianae[J]. J Am Chem Soc, 2016, 138: 4219-4228.
[23]
Yang H , Wang Y , Zhang Z et al . Whole-genome shotgun assembly and analysis of the genome of Shiraia sp. strain Slf14, a novel endophytic fungus producing huperzine A and hypocrellin A[J]. Genome Announc, 2014, 2: e00011-e00014. https://pubmed.ncbi.nlm.nih.gov/24503982/
[24]
Chooi YH , Zhang G , Hu J et al . Functional genomics-guided discovery of a light-activated phytotoxin in the wheat pathogen Parastagonospora nodorum via pathway activation[J]. Environ Microbiol, 2017, 19: 1975-1986.
[25]
Hu J , Sarrami F , Li H et al . Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system[J]. Chem Sci, 2018, 10: 1457-1465. https://pubmed.ncbi.nlm.nih.gov/30809363/
[26]
Fang LZ , Qing C , Shao HJ et al . Hypocrellin D, a cytotoxic fungal pigment from fruiting bodies of the ascomycete Shiraia bambusicola[J]. J Antibiot, 2006, 59: 351-354.
[27]
Yaegashi J , Oakley BR , Wang CC . Recent advances in genome mining of secondary metabolite biosynthetic gene clusters and the development of heterologous expression systems in Aspergillus nidulans[J]. J Ind Microbiol Biot, 2014, 41: 433-442.
2020年第55卷第7期
PDF下载
123
32
引用本文
BibTeX
文章信息
doi: 10.16438/j.0513-4870.2020-0698
  • 接收时间：2020-05-08
  • 首发时间：2026-01-21
  • 出版时间：2020-07-12
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2020-05-08
  • 修回日期：2020-06-06
基金
科技部“重大新药创制”科技重大专项(2018ZX09711001-008-001)
中国医学科学院医学与健康科技创新工程(2017-I2M-4-004)
作者信息
    1.中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050
    2.沈阳药科大学中药学院, 辽宁 沈阳 110016

通讯作者:

*胡友财, E-mail:
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/yxxb/CN/10.16438/j.0513-4870.2020-0698
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62199257
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持