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Efficient production of 2,3-butanediol in Saccharomyces cerevisiae by eliminating ethanol and glycerol production and redox rebalancing
- Kim, Sujin, Hahn, Ji-Sook
- Metabolic engineering 2015 v.31 pp. 94-101
- Bacillus subtilis, Lactococcus lactis, NAD (coenzyme), Saccharomyces cerevisiae, batch fermentation, biochemical pathways, byproducts, ethanol, fuels, glucose, glycerol, redox reactions
- 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 72.9g/L 2,3-butanediol with the highest yield (0.41g/g glucose) and productivity (1.43g/(L·h)) ever reported in S. cerevisiae.