Complete biosynthesis of a sulfated chondroitin in Escherichia coli
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Authors
Badri, Abinaya
Williams, Asher
Awofiranye, Adeola
Datta, Payel
Xia, Ke
He, Wenqin
Fraser, Keith
Dordick, Jonathan S.
Linhardt, Robert J.
Koffas, Mattheos A.G.
Issue Date
2021-12-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
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.
Description
Nature Communications, 12, 1389
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
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.
Publisher
Nature
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
20411723