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用Saccharomyces cerevisiae进行代谢工程,用于生物合成抗癌原前体germacrene A

Xiaokun Wang¹, Ge Yao², Yunfei Zhang²

¹State Key Laboratory of NBC Protection for Civilian, Beijing 102205, People's Republic of China; School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

Bioorganic chemistry

|November 15, 2025

概括

研究人员通过优化其代谢途径,对酵母进行了改造,以产生β-元素,一种癌症药物. 这种可扩展的微生物生产克服了有价值的基的供应限制.

科学领域:

生物技术是生物技术.
代谢工程是代谢工程.
合成生物学合成生物学

背景情况:

β-elemene是一种经过临床批准的抗瘤剂,其天然来源Curcuma wenyujin的丰度较低.
格尔马克林A是β元素的直接前体,在生产中存在瓶.

研究的目的:

开发一种可扩展的微生物生产途径,用于β-元素.
通过增强其在Saccharomyces cerevisiae中的前体合成来克服β-元素的供应瓶.

主要方法:

在Saccharomyces cerevisiae中系统地重新连接美酸盐路径,以扩大C15前体池.
选了19种生殖A合成酶,其中来自Daldinia eschscholtzii的DeGAS显示出高产量.
工程策略包括酶融合 (DeGAS到Farnesyl Pyrophosphate Synthase) 和基因盒三倍化.

主要成果:

确定DeGAS是一种高产量的生殖A合成酶,产生399.8 mg/L.
通过酶融合和磁带三倍化实现了985.5 mg/L的标位.
证明了5L料批生物反应器产量为19.82g/L的生殖基A,比摇瓶培养显著增加.

结论:

建立了一个可扩展的微生物发酵工艺,用于生产β元素.
通过在酵母中使用代谢工程验证了用于基过量生产的可通用策略.

关键词:

基尔马克伦 A 基尔马克伦 A 代谢工程是代谢工程.它们中的一种是S. cerevisiae.合成生物学合成生物学的β-元素.

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