De novo biosynthesis of D-panthenol in engineered E. coli with rationally designed L-homoserine decarboxylase
文献类型: 外文期刊
作者: Peng Zheng;Jie Ren;Jie Zheng;Feixia Liu;Xinhao Han;Bo Yu
作者机构:
关键词: 3-Amino-1-propanol;D-panthenol;Enzyme rational design;L-tyrosine decarboxylase;Metabolic engineering
期刊名称: Metabolic Engineering
ISSN: 1096-7176
年卷期: 2025 年 92 卷
页码:
收录情况: SCIE(2025版) ; ; EI(2025版)
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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