Complete biosynthesis of a sulfated chondroitin in Escherichia coli

Badri, Abinaya
Williams, Asher
Awofiranye, Adeola
Datta, Payel
Xia, Ke
He, Wenqin
Fraser, Keith
Dordick, Jonathan S.
Linhardt, Robert J.
Koffas, Mattheos A.G.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Complete biosynthesis of a sulfated chondroitin in Escherichia coli, A. Badri, A. Williams, A. Awofiranye, P. Datta, K. Xia, W. He, K. Fraser, J. S. Dordick, R. J. Linhardt, M. A. G. Koffas, Nature Communications, 12, 1389, 2021.
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.
Nature Communications, 12, 1389
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Rensselaer Polytechnic Institute, Troy, NY
Nature Communications
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