Enhanced Hyaluronic Acid Production in Bacillus subtilisby Coexpressing Bacterial Hemoglobin.

Bacillus subtilisstrains that can produce hyaluronic acid (HA) were constructed by integrating the HA synthase gene (hasA) and the UDP-glucose dehydrogenase gene of group C Streptococcus(hasB) or of B. subtilisitself (tauD) into the amyE locus of the B. subtilischromosome. All of the inserted genes were under the control of a strong constitutive vegIIpromoter of B. subtilis. Although HA production could be achieved by expressing hasA alone, coexpressing hasB or tauD with hasA could enhance HA production at least 2-fold. To replenish the energy consumed for HA biosynthesis, Vitreoscillahemoglobin (VHb) was coexpressed with the HA-expressing genes. With the expression of VHb, not only the cell concentration was enhanced 25%, but also HA production was further increased by 100%. About 1.8 g/L of HA was obtained by the recombinant strain B. subtiliscarrying VHb, hasA, and tauD genes in the expression cassette after 30 h cultivation. [ABSTRACT FROM AUTHOR]