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 th... More
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 mm (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 mm (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.