Versatile strategies for bioproduction of hyaluronic acid driven by synthetic biology

Abstract Owing to its outstanding water-retention ability, viscoelasticity, biocompatibility and non-immunogenicity, Hyaluronic acid (HA), a natural linear polymer alternating linked by d -glucuronic acid and N-acetylglucosamine, has been widely employed in cosmetic, medical and clinical applications. With the development of synthetic biology and bioprocessing optimization, HA production via microbial fermentation is an economical and sustainable alternative over traditional animal extraction methods. Indeed, recently Streptococci and other recombinant systems for HA synthesis has received increasing interests due to its technical advantages. This review summarizes the production of HA by microorganisms and demonstrates its synthesis mechanism, focusing on the current status in various production systems, as well as common synthetic biology strategies include driving more carbon flux into HA biosynthesis and regulating the molecular weight (MW), and finally discusses the major challenges and prospects.