Microbial hyaluronic acid production in the 21 century: a roadmap toward high production, tailored molecular weight

Abstract

Hyaluronic acid is a biopolymer that has gained attention from both researchers and the public since its discovery in 1934. In 2022, its global annual demand was 667 MT, with a market value of 9.4 billion dollars and an expected compound growth rate of 7.7% from 2024 and 2030. Such popularity lies in its many applications, which ranges from pharmaceutical to Tissue Engineering. Its molecular weight (MW) determines which application hyaluronic acid is better suited for: high MW (over 1 MDa) is used in medical applications such as osteoarthritis and ophthalmology, and low MW (less than 0.05 MDa) are suited for moisturizing cosmeceuticals. This makes hyaluronic acid molecular weight an important parameter for its production. The first industrial process was based on extraction from rooster combs. However, it shifted toward microbial production with Streptococcus zooepidemicus. Studies focus on improving its production and tailoring its molecular weight by accessing optimum temperature, pH, aeration, agitation, carbon, and nitrogen sources concentration and origin. his review aims to provide an overview of the current knowledge on the effects of metabolic and environmental factors in microbial hyaluronic acid production. The review shows that there has been extensive research in optimizing cultivation medium composition, temperature, pH, and aeration between 2018 and 2023, but further studies are required to optimize the metabolism of S. zooepidemicus towards maximum biopolymer production and molecular weight.