Complete biosynthesis of a sulfated chondroitin in Escherichia coli

Abinaya Badri, Asher Williams, Adeola Awofiranye, Payel Datta, Ke Xia, Wenqin He, Keith Fraser, Jonathan S. Dordick, Robert J. Linhardt, Mattheos A.G. Koffas

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Article number1389
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021
Externally publishedYes

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