Development of a cost-effective process for hyaluronic acid production in bacillus subtilis

CERMINATI, SEBASTIAN; ANSELMI PABLO; LACAVA FRANCO; MARCHISIO, FIORELA; HAILS, GUILLERMO; PAOLETTI, LUCIANA; AGUIRRE, ANDRES; PEIRÚ SALVADOR; CASTELLI, MARÍA EUGENIA; MENZELLA, HUGO G.

Online

Congreso; 56th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2020

In the last decades, the development of genetic tools for metabolic pathway engineering along with robust fermentation technologies facilitated cost-efficient manufacturing processes of relevant industrial products. An appealing target for this technologies is hyaluronic acid (HA), a high value glycosaminoglycan (GAG) required for food, cosmetic, orthopedic and healthcare applications. HA is a linear unbranched high-molecular-weight GAG, composed of repeated N-acetylglucosamine and glucuronic acid units. Today, it is mainly obtained from certain attenuated strains of the Streptococcus group C grown in complex media, composed of materials with an inherent inconsistent quality. The resulting manufacturing processes, are therefore costly and require multiple operations to isolate pure HA. Here, a detailed description of the development of a scalable process for the production of HA in Bacillus subtilis grown in chemically defined media is reported. The volumetric productivity achieved here is one order of magnitude higher than those obtained with salt based media. A comparative analysis shows that HA with an average MW above 1 MDa can be manufactured at lower costs than those of previously reported methods. Moreover, the medium and fermentation procedure described here represents an adaptable platform for the cost-effective production of other biomolecules in B. subtilis heterotrophic strains