Microbial production of hyaluronic acid: The current advances, engineering strategies and trends

Hyaluronic acid (HA) is a versatile biomolecule with applications in medicine, cosmetics, and pharmaceuticals. While traditionally extracted from animal tissues, HA is now predominantly produced through microbial fermentation. Microbial fermentation using strains such as Streptococcus zooepidemicus, Corynebacterium glutamicum, and Bacillus subtilis offers a more scalable and sustainable alternative to chemical and animal extraction methods. Recent studies reveal promising yields from engineered strains of Corynebacterium glutamicum and Bacillus subtilis, utilizing advanced metabolic and genetic techniques. Recent advancements in genetic and metabolic engineering, as well as synthetic biology, have addressed some challenges related to molecular weight, viscosity, and by-product formation. This review focuses on the microbial production of HA using engineered strains, encompassing producer organisms, metabolic engineering strategies, industrial-scale production, and key factors influencing molecular weight. Furthermore, it addresses the challenges and potential solutions associated with HA production. Additional research is necessary to develop more efficient and robust engineered strains that exhibit resistance to contamination and can utilize low-cost substrates, such as Pseudomonas putida and Halomonas spp. By overcoming these challenges, researchers can advance the industrial production of HA and expand its applications, thereby contributing to the growth of the HA market.