Microbial production and metabolic engineering of chondroitin and chondroitin sulfate

Abstract

Several commercial uses and potential novel applications have recently been described for chondroitin sulfate (CS). However, the currently applied animal extractive procedure has a high environmental impact, which may become more profound especially in relation to the forecasted expansion of the CS market for applications as a food supplement, pharmaceutical ingredient, and biopolymer in materials for regenerative medicine. This issue, together with religious and consumer concerns, has prompted the good manufacturing practice (GMP) of chondroitin and CS. This is achievable by combining the design of metabolically engineered microorganisms and tailor-made fermentation processes with semi-synthetic or enzyme-based approaches. The final target is to obtain molecules with specific sulfation patterns that resemble those occurring in natural products and improve the sulfation motif or introduce specific substitutions, such as fucosylation, to tune the biological function. The frontier that is currently triggering attention is related to evaluating the bioactivity of unsulfated chondroitin. Due to recent advancements in the field, a brief survey of the most recent patent and research literature is discussed here.