Insight into hyaluronic acid molecular weight control

Hyaluronic acid (HA) is a ubiquitous polysaccharide found in humans, animals, bacteria, algae and molluscs. Simple yet sophisticated, HA demonstrates unique and valuable rheological properties. In solution, HA behaves as a stiffened random coil and the resultant behaviour, even at low concentrations, is far from Newtonian or ‘ideal’. These rheological properties are heavily influenced by molecular weight (MW), so it is not surprising that many of the biological functions of HA are dependent on molecular size. The current billion dollar market for HA continues to grow rapidly, both in gross production and the number of applications for its use. Increasing demand, in conjunction with a reticence to use animal-derived HA, has revitalised the market for HA produced by bacterial fermentation. Although the genes and pathways involved in bacterial production of HA are well characterised, the mechanisms that underlie HA MW control are less well understood. By performing a thorough analysis of the proposed mechanisms of MW control in bacterial fermentation, this mini-review tries to elucidate the challenges and future directions for bacterial HA biosynthesis.