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 and Mattheos A. G. Koffas ()
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Abinaya Badri: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute
Asher Williams: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute
Adeola Awofiranye: Department of Biological Sciences, Rensselaer Polytechnic Institute
Payel Datta: Department of Biological Sciences, Rensselaer Polytechnic Institute
Ke Xia: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute
Wenqin He: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute
Keith Fraser: Department of Biological Sciences, Rensselaer Polytechnic Institute
Jonathan S. Dordick: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute
Robert J. Linhardt: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute
Mattheos A. G. Koffas: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21692-5

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DOI: 10.1038/s41467-021-21692-5

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