Microbial Hyaluronic Acid Biosynthesis
Esteban Marcellin, Wendy Chen and Lars Keld Nielsen
from: Microbial Production of Biopolymers and Polymer Precursors: Applications and Perspectives (Edited by: Bernd H. A. Rehm). Caister Academic Press, U.K. (2009)
Hyaluronic acid (HA) is a biopolymer with valuable applications in the pharmaceutical and cosmetic industry. Currently, HA is produced commercially by either extraction from animal tissues i.e. rooster comb or bacterial fermentation. Increased concerns over the contamination of animal derived products with infectious agents have made bacterial fermentation a more desirable production system to meet future demands. The high viscosity of HA dictates low titres of 5-10 g/L, a level readily achieved through batch fermentation of Group C streptococci. Substrate cost is a minor factor for this high value polymer, hence strain and process development has focused on improving quality, in particular molecular weight. Little is known about what controls molecular weight of beta-polysaccharides such as HA. This is even true for abundant beta-polysaccharides such as chitin and cellulose. Several groups including ours have pursued various hypotheses for the past decade, but no hypothesis has captured the Mw regulation observed in bioreactors. The HA synthase is responsible for all steps in polymerisation and most likely also translocation. In vitro studies have identified several residues essential for high molecular weight and maximum molecular weight appears to be an intrinsic feature of the synthase. The actual molecular weight realised in fermentation, however, depends on fermentation conditions. In general, high molecular weight is observed under conditions with excess resources. Surprisingly, however, preliminary studies cannot relate these findings to higher levels of the UDP-sugars used in biosynthesis. Metabolic engineering and the recent advance in omics technologies are providing new opportunities. Heterologous hosts such as B. subtilis, L. lactis, and E. coli have been successfully engineered to produce HA and may prove more amenable to engineering high molecular weight HA read more ...