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
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)