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

文献类型： 外文期刊

作者： Zheng, Peng 1 ; Ren, Jie 2 ; Zheng, Jie 1 ; Liu, Feixia 1 ; Han, Xinhao 5 ; Yu, Bo 1 ;

作者机构： 1.Chinese Acad Sci, Inst Microbiol, Dept Microbial Physiol & Metab Engn, State Key Lab Microbial Divers & Innovat Utilizat, Beijing 100101, Peoples R China

2.Chinese Acad Agr Sci, State Key Lab Biol Plant Dis & Insect Pests, Inst Plant Protect, Beijing 100029, Peoples R China

3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

4.Beijing Key Lab Genet Element Biosourcing & Intell, Beijing 100101, Peoples R China

5.Beijing Neobinder Co Ltd, Beijing 100094, Peoples R China

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

页码：

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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