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长期依赖珍稀植物提取的抗癌药原料,有望找到新的微生物制造路径。首都医科大学中医药学院胡雅婷团队联合中国中医科学院黄璐琦团队,通过改造酿酒酵母,实现了依托泊苷和替尼泊苷共同直接前体的从头生物合成。2026年7月30日,相关成果发表于《Science》。

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(图片来源:英国皇家园艺学会)

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珍稀植物抗癌成分实现酵母合成
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长期依赖珍稀植物提取的抗癌药原料,有望找到新的微生物制造路径。首都医科大学中医药学院胡雅婷团队联合中国中医科学院黄璐琦团队,通过改造酿酒酵母,实现了依托泊苷和替尼泊苷共同直接前体的从头生物合成。2026年7月30日,相关成果发表于《Science》。

. 珍稀植物抗癌成分实现酵母合成. 科技导报, 2026 , 44 (15) : 3 -3 .
. Science & Technology Review, 2026 , 44 (15) : 3 -3 .
长期依赖珍稀植物提取的抗癌药原料,有望找到新的微生物制造路径。首都医科大学中医药学院胡雅婷团队联合中国中医科学院黄璐琦团队,通过改造酿酒酵母,实现了依托泊苷和替尼泊苷共同直接前体的从头生物合成。2026年7月30日,相关成果发表于《Science》。
依托泊苷是小细胞肺癌等肿瘤治疗的重要药物,替尼泊苷则用于白血病和部分脑肿瘤治疗。目前,2种药物的生产仍依赖鬼臼毒素类天然产物,其中重要来源之一是生长于喜马拉雅地区的珍稀濒危植物桃儿七。由于野生资源有限、植物生长缓慢且人工栽培受到环境条件限制,相关药物原料的稳定供应长期面临资源压力。
研究的难点在于,鬼臼毒素类木脂素的形成需要经历前体供应、立体选择性二聚、复杂骨架构建以及多步氧化和糖基化等反应,要把这一整套植物天然产物合成过程“搬进”酵母并不容易。研究人员首先利用羧酸还原酶在酵母中重构松柏醇前体供给途径,并将其与立体选择性二聚反应耦合;随后引入芳基四氢萘类木脂素骨架合成酶,使酵母能够从头形成(-)-去氧鬼臼毒素等核心骨架;再利用多个植物来源的细胞色素P450和糖基转移酶,对骨架进行不同位点的氧化和糖基化修饰。其中,一个关键瓶颈是糖基化。团队通过基因组挖掘和功能筛选鉴定出糖基转移酶UGT709AX1,使鬼臼毒素类分子能够在C-4位直接完成酶促糖基化,为获得依托泊苷和替尼泊苷的直接糖苷前体补上了关键一步。
围绕上述多个环节,研究人员进一步重新设计酵母代谢网络,在单一细胞中完成60余次基因编辑,引入涉及45种异源酶的合成体系,最终使酵母能够从简单碳源出发,实验室发酵约3天即可获得目标前体。
(综合:《Science》、首都医科大学官网、科学网)

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  • 首发时间:2026-08-31
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

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
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