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

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.