A microbial–enzymatic strategy for producing chondroitin sulfate glycosaminoglycans

Chondroitin sulfate has been widely used in both medical and clinical applications. Commercial chondroitin sulfate has been mainly acquired from animal tissue extraction. Here we report a new two-step biological strategy for producing chondroitin sulfate A and chondroitin sulfate C. First, the chondroitin biosynthesis pathway in a recombinant Bacillus subtilis strain using sucrose as carbon source was systematically optimized and the titer of chondroitin was significantly enhanced to 7.15 g/L. Then, specific sulfation transformation systems were successfully constructed and optimized by combining the purified aryl sulfotransferase IV (ASST IV), chondroitin 4-sulfotransferase (C4ST) and chondroitin 6-sulfotransferase (C6ST). Chondroitin sulfate A and C were enzymatically transformed from chondroitin at conversion rates of 98% and 96%, respectively. The present biological strategy has great potential to be scaled up for biosynthesis of chondroitin sulfate A and C from cheap carbon sources.