Biotechnological production of hyaluronic acid: a mini review

Abstract

Hyaluronic acid (HA) is a polysaccharide found in the extracellular matrix of vertebrate epithelial, neural and connective tissues. Due to the high moisture retention, biocompatibility and viscoelasticity properties of this polymer, HA has become an important component of major pharmaceutical, biomedical and cosmetic products with high commercial value worldwide. Currently, large scale production of HA involves extraction from animal tissues as well as the use of bacterial expression systems in Streptococci. However, due to concerns over safety, alternative sources of HA have been pursued which include the use of endotoxin-free microorganisms such as Bacilli and Escherichia coli. In this review, we explore current knowledge of biosynthetic enzymes that produce HA, how these systems have been used commercially to produce HA and how the challenges of producing HA cheaply and safely are being addressed.

Identification and Comparison of Hyaluronic Acid Biosynthetic Genes from Different Capsular Types of Pasteurella Multocida

“…The hyaluronic acid biosynthesis pathway of P. multocida involves nine enzyme-encoding genes, including glck, pgi, pgm, galU, hyaC, glmS, glmM, glmU and hyaD, similar to the capsular polysaccharide biosynthesis pathway in S. pyogenes [19,[25][26][27]. HAs are known to be primary capsular components of type A strains of P. multocida.…”

“…Comparative analysis of the HA biosynthetic genes from various organisms showed that the hyaluronan synthase from P. multocida was the only class II enzyme, while other organisms produced the class I hyaluronan synthase [17]. Class II hyaluronan synthases are different from class I hyaluronan synthases in terms of structural topology and biosynthesis mechanism [18,19]. In this step, the HA synthesized by class II hyaluronan synthases is connected to the cytoplasmic membrane and transported through the membrane directly to the extracellular matrix during chain elongation and not sulfated or chemically modi ed after biosynthesis [17,20,21].…”

“…HA synthesis has been studied in many other microorganisms (Bacillus sp., Lactococcus sp., and Escherichia. coli) for the production of high-quality and safe-to-use HAs [16,19]. Industrial-scale HA production was developed with recombinant E. coli and Bacillus sp.…”

Glycolysis and Its Metabolic Engineering Applications

“…24 Hyaluronic acid (HA) is a glucuronic acidderived polysaccharide discovered in many animal tissues, which has remarkable applications in pharmaceutical, biomedical, and cosmetic products with high commercial value. 25 Largescale production of HA has focused on direct extraction from animal tissues and the use of bacterial expression systems in Streptococci. 25 E. coli has also been developed as a microbial factory for HA production via expression of hyaluronic acid synthase (HAS) gene from Streptococcus pyogenes, UDPglucose 6dehygrogenase (Ugd), Glucose1P uridyltransferase (GalF), and Nacetyl glucosamine uridyl transferase (GlmU) from E. coli (Figure 1.1).…”

“…25 Largescale production of HA has focused on direct extraction from animal tissues and the use of bacterial expression systems in Streptococci. 25 E. coli has also been developed as a microbial factory for HA production via expression of hyaluronic acid synthase (HAS) gene from Streptococcus pyogenes, UDPglucose 6dehygrogenase (Ugd), Glucose1P uridyltransferase (GalF), and Nacetyl glucosamine uridyl transferase (GlmU) from E. coli (Figure 1.1). 26 Heparin and heparan sulfate (HS), chondroitin, and chondroitin sulfate are important glycosamino glycan biopolymers commonly used in pharmaceutical applications owing to their anticoagulation, antiinflammatory, anticancer, antimeta static, and antiangiogenic properties.…”