Metabolic Engineering of for the Production of Hyaluronic Acid From Glucose and Galactose.

Hyaluronic acid is a glycosaminoglycan biopolymer widely present throughout connective and epithelial tissue, and has been of great interest for medical and cosmetic applications. In the microbial production of hyaluronic acid, it has not been established to utilize galactose enabling to be converted to UDP-glucuronic acid, which is a precursor for hyaluronic acid biosynthesis. In this study, we engineered to produce hyaluronic acid from glucose and galactose. The galactose-utilizing Leloir pathway was activated by knocking out the and genes encoding the transcriptional repressors. Also, the gene from was introduced for the expression of hyaluronic acid synthase. The consumption rates of glucose and galactose were modulated by knockout of the and genes, which encode 6-phosphofructokinase I and glucose-6-phosphate dehydrogenase, respectively. Furthermore, the precursor biosynthesis pathway for hyaluronic acid production was manipulated by separately overexpressing the gene clusters and , which enable the production of UDP-glucuronic acid and UDP--acetyl-glucosamine, respectively. Batch culture of the final engineered strain produced 29.98 mg/L of hyaluronic acid from glucose and galactose. As a proof of concept, this study demonstrated the production of hyaluronic acid from glucose and galactose in the engineered .