Prospective bacterial and fungal sources of hyaluronic acid: A review

Abstract

The unique biological and rheological properties make hyaluronic acid a sought-after material for medicine and cosmetology. Due to very high purity requirements for hyaluronic acid in medical applications, the profitability of streptococcal fermentation is reduced. Production of hyaluronic acid by recombinant systems is considered a promising alternative. Variations in combinations of expressed genes and fermentation conditions alter the yield and molecular weight of produced hyaluronic acid. This review is devoted to the current state of hyaluronic acid production by recombinant bacterial and fungal organisms.

Keywords: ATP, adenosine triphosphate; CSDB, Carbohydrate Structure Database; DO, dissolved oxygen; FDA, Food and Drug administration; GAG, glycosaminoglycan; GRAS, generally recognized as safe; Glc, glucose; GlcpA, glucuronic acid; GlcpNAc, N-acetylglucosamine; Gram-positive bacteria; HA, hyaluronic acid; HAS, hyaluronic acid synthase; HW HA, high-molecular weight hyaluronic acid; HYBID, hyaluronan-binding protein involved in HA depolymerization; Hyaluronic acid; LW HA, low-molecular weight hyaluronic acid; MMP-2, matrix metalloproteinase 2; MW, molecular weight; Microbial fermentation; MurNAc, N-acetylmuramic acid; ND, no data; RHAMM, receptor for hyaluronic acid mediated motility; Recombinant organism; SNFG, symbol nomenclature for glycans; UDP, uridine 5′-trihydrogen diphosphate; UMP, 5′-uridylic acid; UTP, uridine-5′-triphosphate; amyE, α-amylase (B. subtilis); aprE, subtilisin E (B. subtilis); araR, repressor of arabinose operons; cat, acetyl-CoA:CoA transferase; dcas9, dead Cas9 (derived from S. pyogenes); eglS, endoglucanase (B. subtilis); epr, minor extracellular protease (B. subtilis); galR, HTH-type transcriptional regulator GalR (E. coli); galS, HTH-type transcriptional regulator GalS (E. coli); galU, UTP-glucose-1-phosphate uridylyltransferase; glmM, phosphoglucosamine mutase; glmS, l-glutamine-d-fructose-6-phosphate aminotransferase; glmU, bifunctional UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase (Corynebacterium glutamicum); kfiD, UDP-glucose 6-dehydrogenase; lacA (ganA), β-galactosidase (B. subtilis); ldh, lactate dehydrogenase; mazF, endoribonuclease (E. coli); mpr, extracellular metalloprotease (B. subtilis); nprB, neutral protease B (B. subtilis); nprE, bacillolysin (B. subtilis); pfkA, ATP-dependent 6-phosphofructokinase (E. coli); pgcA, phosphoglucomutase; poxB, pyruvate:quinone oxidoreductase; pta-ackA operon, phosphate acetyltransferase and acetate kinase; sigF, RNA polymerase sigma-F factor (B. subtilis); thrC, threonine synthase (B. subtilis); tuaD, UDP-glucose 6-dehydrogenase (1); udgA, UDP-glucose 6-dehydrogenase (2); upp, uracil phosphoribosyltransferase (B. subtilis); vHMW HA, very-high-molecular weight hyaluronic acid; wprA, cell wall associated protease (B. subtilis); xylR, xylose operon repressor (B. megaterium); zwf, glucose-6-phosphate 1-dehydrogenase.