Engineering microorganisms for the efficient synthesis of capsular polysaccharides and related enzymes

Abstract

Heparin and chondroitin sulfate (CS) are glycosaminoglycans (GAGs) with many biological and physiological functions that contribute to their widespread utilization as anticoagulants and anti-inflammatory drugs. These sulfated polysaccharides are primarily extracted and purified from animal tissues, where factors such as source material, manufacturing processes, and the presence of contaminants impact overall safety and biological and pharmacological efficacy. The past few years have seen an increased interest in the development of alternative GAG production methods, including chemical and chemo-enzymatic synthesis and biosynthesis from GAG-producing cells. As part of ongoing efforts to separate the food chain from the drug chain, we are engineering microbial metabolism in order to produce CS in Escherichia coli, and heparosan, a valuable precursor to heparin, in Bacillus megaterium.