Costunolide, the simplest sesquiterpene lactone, has potent anti-inflammatory and antitumor properties and has been investigated 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 utilizing 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.
YANG Bonan
,
LIU Chunli
,
HAO Yunpeng
,
XU Guangbo
,
LIU Xiuxia
,
YANG Yankun
,
BAI Zhonghu
. Metabolic engineering Escherichia coli for de novo biosynthesis of costunolide[J]. Food and Fermentation Industries, 2025
, 51(20)
: 77
-83
.
DOI: 10.13995/j.cnki.11-1802/ts.042101
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