| Summary: | Chondroitin sulfate (CS) is widely used across the world as a nutraceutical and pharmaceutical. Its high demand and potential limitations in current methods of extraction call for an alternative method of production. This review highlights glycosaminoglycan’s structure, its medical significance, animal extraction source, and the disadvantages of the extraction process. We cover alternative production strategies for CS and its precursor, chondroitin. We highlight chemical synthesis, chemoenzymatic synthesis, and extensively discuss how strains have been successfully metabolically engineered to synthesize chondroitin and chondroitin sulfate. We present microbial engineering as the best option for modern chondroitin and CS production. We also explore the biosynthetic pathway for chondroitin production in multiple microbes such as <i>Escherichia coli</i>, <i>Bacillus subtilis</i>, and <i>Corynebacterium glutamicum</i>. Lastly, we outline how the manipulation of pathway genes has led to the biosynthesis of chondroitin derivatives.
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