Engineering New‐to‐Nature Biological Pathways for β,γ‐Alkanediol Synthesis

ABSTRACT β,γ‐Alkanediols are value‐added chemicals that can be used as functional solvents, biofuels, and cosmetic components. Although some linear chain β,γ‐alkanediols beside butane‐2,3‐diol are naturally present, their biosynthetic pathways remain underexplored. In this study, we expand the acetohydroxyacid synthase (AHAS)‐mediated carboligation for the synthesis of linear chain β,γ‐alkanediols in Escherichia coli , namely, hexane‐2,3‐diol (2,3‐HDO) and pentane‐2,3‐diol (2,3‐PDO). Two pathways for the production of 2,3‐HDO (a redesigned Clostridium ‐derived clostridial pathway and an artificial reversal β‐oxidation pathway) were developed, and the engineered E. coli cells with further disruption of endogenous thioesterases produced 152.2 m m (17.98 g/L) 2,3‐HDO from 60.03 g/L glucose in the fed‐batch bioreactor. We also expand the similar design for 2,3‐PDO biosynthesis, achieving 15.5 m m (1.61 g/L) in shake flasks. This work demonstrates the great versatility of the AHAS‐mediated carboligation for the synthesis of linear chain β,γ‐alkanediols, which would pave its way for the future production of other linear chain β,γ‐diols from renewable feedstocks.