Complete biosynthesis of a sulfated chondroitin in Escherichia coli

Nat Commun. 2021 Mar 2;12(1):1389. doi: 10.1038/s41467-021-21692-5.

Abstract

Sulfated glycosaminoglycans (GAGs) are a class of important biologics that are currently manufactured by extraction from animal tissues. Although such methods are unsustainable and prone to contamination, animal-free production methods have not emerged as competitive alternatives due to complexities in scale-up, requirement for multiple stages and cost of co-factors and purification. Here, we demonstrate the development of single microbial cell factories capable of complete, one-step biosynthesis of chondroitin sulfate (CS), a type of GAG. We engineer E. coli to produce all three required components for CS production-chondroitin, sulfate donor and sulfotransferase. In this way, we achieve intracellular CS production of ~27 μg/g dry-cell-weight with about 96% of the disaccharides sulfated. We further explore four different factors that can affect the sulfation levels of this microbial product. Overall, this is a demonstration of simple, one-step microbial production of a sulfated GAG and marks an important step in the animal-free production of these molecules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biological Transport
  • Biosynthetic Pathways*
  • Chondroitin Sulfates / biosynthesis*
  • Escherichia coli / enzymology
  • Escherichia coli / metabolism*
  • Fermentation
  • Oxidoreductases / metabolism
  • Sulfotransferases / metabolism

Substances

  • Chondroitin Sulfates
  • Oxidoreductases
  • 3'-phosphoadenylyl-5'-phosphosulfate reductase
  • Sulfotransferases