title: Efficient production of 2,3-butanediol in Saccharomyces cerevisiae by eliminating ethanol and glycerol production and redox rebalancing.
abstract: 2,3-Butanediol is a promising valuable chemical that can be used in various areas as a liquid fuel and a platform chemical. Here, 2,3-butanediol production in Saccharomyces cerevisiae was improved stepwise by eliminating byproduct formation and redox rebalancing. By introducing heterologous 2,3-butanediol biosynthetic pathway and deleting competing pathways producing ethanol and glycerol, metabolic flux was successfully redirected to 2,3-butanediol. In addition, the resulting redox cofactor imbalance was restored by overexpressing water-forming NADH oxidase (NoxE) from Lactococcus lactis. In a flask fed-batch fermentation with optimized conditions, the engineered adh1Δadh2Δadh3Δadh4Δadh5Δgpd1Δgpd2Δ strain overexpressing Bacillus subtilis α-acetolactate synthase (AlsS) and α-acetolactate decarboxylase (AlsD), S. cerevisiae 2,3-butanediol dehydrogenase (Bdh1), and L. lactis NoxE from a single multigene-expression vector produced 72.9 g/L 2,3-butanediol with the highest yield (0.41 g/g glucose) and productivity (1.43 g/(L · h)) ever reported in S. cerevisiae.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Kim
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-744, Republic of Korea. Electronic address: hahnjs@snu.ac.kr.
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Hahn
mesh_terms: D002072:Butylene Glycols / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D005285:Fermentation; D005990:Glycerol / Q000378:metabolism*; D060847:Metabolic Engineering; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D002072:Butylene Glycols; D009097:Multienzyme Complexes; D000431:Ethanol; C026978:2,3-butylene glycol; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D005990:Glycerol
keywords: 2,3-Butanediol; Alcohol dehydrogenase; Glycerol-3-phosphate dehydrogenase; NADH oxidase; Saccharomyces cerevisiae