Fermentative High-Level Production of 5‑Hydroxyvaleric Acid by Metabolically Engineered Corynebacterium glutamicum

We report metabolic engineering of Corynebacterium glutamicum (C. glutamicum) for high-level production of 5-hydroxyvaleric acid (5-HV), an important C5 platform chemical covering a wide range of industrial applications, using glucose as a sole carbon source. To derive 5-HV, an artificial 5-HV biosynthesis pathway, composed of the first three reaction steps of an l-lysine catabolic pathway via 5-aminovaleramide along with a subsequent intracellular reduction step, was constructed: l-lysine was converted to glutarate semialdehyde through an l-lysine catabolic pathway encoded by Pseudomonas putida davTBA genes, and glutarate semialdehyde was further reduced to 5-HV by a suitable aldehyde reductase. Various aldehyde reductases including CpnD from Clostridium aminovalericum, Gbd from Ralstonia eutropha, ButA from C. glutamicum, and YihU, YahK, and YqhD from Escherichia coli were examined for efficient 5-HV production through the flask and batch cultivations, and YahK was determined to be the most appropriate aldehyde reductase. Further modification to enhance 5-HV production was investigated by deletion of an endogenous gabD gene responsible for the oxidation of glutarate semialdehyde into glutaric acid in order to suppress glutaric acid by-production. Finally, 52.1 g/L 5-HV with the yield of 0.33 g/g glucose was achieved by fed-batch fermentation of the engineered C. glutamicum with overexpression of davTBA genes and the yahK gene along with gabD deletion in the chromosome.