De novo biosynthesis of D-panthenol in engineered E. coli with rationally L-homoserine

文献类型: 外文期刊

第一作者: Zheng, Peng

作者: Zheng, Peng;Zheng, Jie;Liu, Feixia;Yu, Bo;Ren, Jie;Zheng, Peng;Zheng, Jie;Liu, Feixia;Liu, Feixia;Yu, Bo;Han, Xinhao

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关键词: D-panthenol; 3-Amino-1-propanol; L -tyrosine decarboxylase; Enzyme rational design; Metabolic engineering

期刊名称:METABOLIC ENGINEERING ( 影响因子:6.8; 五年影响因子:7.8 )

ISSN: 1096-7176

年卷期: 2025 年 92 卷

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收录情况: SCI

摘要: D-panthenol is a compound of significant importance in the pharmaceutical, cosmetic, and nutraceutical sectors, attributed to its remarkable moisturizing, anti-inflammatory, and tissue repair properties. Traditional chemical synthesis encounters several challenges, including the generation of toxic by-products, low enantiomeric excess, and expensive purification processes. To date, complete biosynthesis of D-panthenol solely from glucose has seldom been documented. In this study, we have developed a new fermentative route to produce D-panthenol. The pathway incorporates previously unreported reaction of decarboxylating L-homoserine to 3-amino-1-propanol, which is achieved by rational design of a novel tyrosine decarboxylase mutant, informed by structural and mechanistic insights into enzymes acting on sterically similar substrates. The next enzyme facilitating the condensation of 3-amino-1-propanol with D-pantoate for D-panthenol formation was identified through a comprehensive screening of natural D-pantothenate synthetases. The artificial pathway was functionally expressed in a minimally engineered E. coli strain, resulting in the de novo production of D-panthenol from glucose. This research highlights a demonstration of an unnatural enzymatic synthesis process for D-panthenol. With further strain and process engineering, this new approach could be a promising way to produce D-panthenol biologically.

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