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代谢工程改造大肠杆菌从头合成木香烃内酯

杨博楠 刘春立 郝云鹏 许广博 刘秀霞 杨艳坤 白仲虎

食品与发酵工业2025,Vol.51Issue(20):77-83,7.
食品与发酵工业2025,Vol.51Issue(20):77-83,7.DOI:10.13995/j.cnki.11-1802/ts.042101

代谢工程改造大肠杆菌从头合成木香烃内酯

Metabolic engineering Escherichia coli for de novo biosynthesis of costunolide

杨博楠 1刘春立 1郝云鹏 1许广博 1刘秀霞 1杨艳坤 1白仲虎1

作者信息

  • 1. 江南大学生物工程学院,工业生物技术教育部重点实验室,江苏无锡,214122||江南大学,粮食发酵与食品生物制造国家工程研究中心,江苏无锡,214122||江南大学,江苏省生物活性制品加工工程技术研究中心,江苏无锡,214122
  • 折叠

摘要

Abstract

Costunolide,the simplest sesquiterpene lactone,has potent anti-inflammatory and antitumor properties and has been investi-gated as a potential anticancer agent for various tumors in recent years.However,conventional acquisition methods such as chemical synthesis and plant extraction have proven inadequate to meet the demand for sustainable development.Consequently,the synthesis of costunolide using microbial cell factories has emerged as a viable alternative.This study successfully constructed the costunolide biosynthesis pathway by utili-zing Escherichia coli BL21(DE3)as the host organism and glucose as the carbon source,overexpressing the enzyme germacrene A synthase,germacrene A oxidase,costunolide synthase,the cytochrome P450 reductase,and introducing the exogenous mevalonate pathway.Through a series of strategies including screening of expression system and costunolide synthase,supplementation with heme precursors,introduction of metabolically engineered strains,optimization of fermentation conditions,and final produced 6.19 mg/L costunolide in shake flasks,which represents an 81-fold increase compared with the starting strain.The results demonstrated the feasibility of utilizing microbial bacterial cell factories for the synthesis of costunolide and provided a reference strategy for the synthesis of other sesquiterpene lactones.

关键词

大肠杆菌/木香烃内酯/代谢工程/细胞色素P450/萜类化合物

Key words

Escherichia coli/costunolide/metabolic engineering/cytochrome P450/terpenoid

引用本文复制引用

杨博楠,刘春立,郝云鹏,许广博,刘秀霞,杨艳坤,白仲虎..代谢工程改造大肠杆菌从头合成木香烃内酯[J].食品与发酵工业,2025,51(20):77-83,7.

基金项目

国家自然科学青年基金项目(32200092) (32200092)

食品与发酵工业

OA北大核心

0253-990X

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