Hyaluronic acid production by recombinant Lactococcus lactis

Microbial hyaluronic acid (HA), commonly produced by pathogenic Streptococcus, was made possible to be produced by a generally recognized as safe Lactococcus lactis by coexpressing HA synthase and uridine diphosphate-glucose dehydrogenase (UDP-GlcDH) of Streptococcus equi subsp. zooepidemicus in a nisin-controlled expression (NICE) system. With scarce expressed HA synthase alone, the constructed recombinant L. lactis (LL-NA) strain could produce HA with a concentration about 0.08 g/l in the M17 medium supplemented with 1% (w/v) glucose. In contrast to HA synthase, UDP-GlcDH of Streptococcus could be overexpressed in the NICE system. With coexpression of heterologous UDP-GlcDH with HA synthase, the constructed LL-NAB strain grew slightly slower to a concentration about 10% lower that of the LL-NA strain. However, the HA concentration produced was enhanced about eightfold to 0.65 g/l.