Article(id=1315696210913116215, tenantId=1146029695717560320, journalId=1315121759093096577, issueId=1315696195121558078, articleNumber=null, orderNo=null, doi=10.3969/j.issn.1005-7021.2026.04.009, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1763308800000, receivedDateStr=2025-11-17, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1791616021134, onlineDateStr=2026-10-10, pubDate=1787155200000, pubDateStr=2026-08-20, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1791616021134, onlineIssueDateStr=2026-10-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1791616021134, creator=13701087609, updateTime=1791616021134, updator=13701087609, issue=Issue{id=1315696195121558078, tenantId=1146029695717560320, journalId=1315121759093096577, year='2026', volume='46', issue='4', pageStart='1', pageEnd='144', issueExtLink='null', onlineDate='null', pubDate='1787155200000', pubDateStr='2026-08-20', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1791616017369, creator='13701087609', updateTime=1791616161314, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1315696798950339227, tenantId=1146029695717560320, journalId=1315121759093096577, issueId=1315696195121558078, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1315696798950339228, tenantId=1146029695717560320, journalId=1315121759093096577, issueId=1315696195121558078, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=116, endPage=127, ext={EN=ArticleExt(id=1315696211340935224, articleId=1315696210913116215, tenantId=1146029695717560320, journalId=1315121759093096577, language=EN, title=Research Progress on the Metabolic Engineering Modification of Nucleoside-Producing Bacteria, columnId=null, journalTitle=Journal of Microbiology, columnName=null, runingTitle=null, highlight=null, articleAbstract=

Nucleosides, as the basic structural units of nucleic acid molecules and important biological regulatory factors, have demonstrated extensive application value in multiple fields such as medicine, food, and chemical engineering. Nucleosides' biosynthesis mainly take place through two pathways of de novo synthesis and salvage synthesis. In recent years, with the rapid development of synthetic biology and metabolic engineering technologies, the production efficiency of nucleosides has been significantly improved through strategies such as relief the metabolic regulation of nucleoside-producing bacteria, enhancement of key enzyme expression, and blocking of competitive and degradation pathways. However, the efficient biosynthesis of nucleosides still faces multiple challenges such as insufficient supply of precursors, feedback inhibition, uneven distribution of metabolic flow, and accumulation of potentially toxic products. This article systematically reviews the biosynthetic pathways of nucleosides and focuses on sorting out the latest research progress on metabolic engineering technology in modifying purine nucleoside (adenosine, guanosine, inosine) and pyrimidine nucleoside (cytidine, uridine, thymidine)-producing bacteria. The article delves deeply into the latest achievements in optimizing nucleoside synthesis pathways, enhancing metabolic fluxes, and increasing product accumulation through advanced strategies such as gene editing (like CRISPR/Cas systems), dynamic regulation, promoter engineering, and efflux protein modification. In addition, this paper also analyzes the regulatory mechanism of nucleosides biosynthesis, and in response to the current bottleneck problems, proposes future research directions and technical prospects, aiming to provide theoretical guidance and strategic references for the development of efficient nucleoside engineering strains, with the expectation of accelerating their industrialization process and meeting the increasingly diversified industrial demands.

, authors=Lu ZHOU¹, Geng-xuan YAN¹, Yun-zhi ZHANG², Chun-yan LIU², Yu-tong LIU³, Hong-fa REN⁴, Shu-mei ZHANG¹, Chong YU¹, Yuan TIAN^{1, *}, authorsList=Lu ZHOU, Geng-xuan YAN, Yun-zhi ZHANG, Chun-yan LIU, Yu-tong LIU, Hong-fa REN, Shu-mei ZHANG, Chong YU, Yuan TIAN, authorCompany=null, correspAuthors=Yuan TIAN, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, 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, fund=null), CN=ArticleExt(id=1315696211697451067, articleId=1315696210913116215, tenantId=1146029695717560320, journalId=1315121759093096577, language=CN, title=核苷产生菌代谢工程改造的研究进展, columnId=1315696198753825373, journalTitle=微生物学杂志, columnName=专题论述, runingTitle=null, highlight=null, articleAbstract=

核苷作为核酸分子的基本结构单元和重要的生物调控因子，在医药、食品和化工等多个领域展现出广泛的应用价值。核苷的生物合成途径主要包括从头合成途径和补救合成途径。近年来，随着合成生物学和代谢工程技术的飞速发展，通过对核苷产生菌进行代谢调控解除、关键酶表达强化以及竞争与降解途径阻断等策略的应用，显著提升了核苷的生产效率。然而，核苷的高效生物合成仍面临前体供应不足、反馈抑制、代谢流分配不均以及潜在毒性产物积累等多重挑战。本文系统综述了核苷的生物合成途径，重点梳理了代谢工程技术在改造嘌呤核苷（腺苷、鸟苷、肌苷）和嘧啶核苷（胞苷、尿苷、胸苷）产生菌方面的最新研究进展，深入探讨了基因编辑（如CRISPR/Cas系统）、动态调控、启动子工程和外排蛋白改造等先进策略，以及优化核苷合成途径、提升代谢通量、增强产物积累所取得的最新成果。同时对核苷生物合成的调控机制进行了剖析，并针对当前面临的瓶颈问题，提出了未来的研究方向和技术展望，旨在为高效核苷工程菌株的开发提供理论指导和策略参考，以期加速其工业化进程，满足日益增长的多元化产业需求。

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