Cofactor engineering for improved production of 2,4-dihydroxybutyric acid via the synthetic homoserine pathway.

ABSTRACT: (L)-2,4-dihydroxybutyrate (DHB) is a versatile compound that can serve as a precursor for the synthesis of the methionine analog 2-hydroxy-4-(methylthio)butyrate and new advanced polymers. We previously implemented in Escherichia coli an artificial biosynthetic pathway for the aerobic production of DHB from glucose, which relies on the deamination of (L)-homoserine followed by the reduction of 2-oxo-4-hydroxybutyrate (OHB) and yields DHB by an enzyme-bearing NADH-dependent OHB reductase activity. Under aerobic conditions, using NADPH as a cofactor is more favorable for reduction processes. We report the construction of an NADPH-dependent OHB reductase and increased intracellular NADPH supply by metabolic engineering to improve DHB production. Key cofactor discriminating positions we

SUBMITTER: Ihle N 

PROVIDER: S-EPMC11882521 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature