Complete biosynthesis of a sulfated chondroitin in Escherichia coli
| Autor: | Ke Xia, Keith Fraser, Asher Williams, Payel Datta, Jonathan S. Dordick, Abinaya Badri, Adeola Awofiranye, Wenqin He, Mattheos A. G. Koffas, Robert J. Linhardt |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Sulfotransferase Science General Physics and Astronomy medicine.disease_cause 01 natural sciences Article General Biochemistry Genetics and Molecular Biology Applied microbiology Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound Sulfation Biosynthesis Escherichia coli medicine Chondroitin Chondroitin sulfate Multidisciplinary 010405 organic chemistry Chondroitin Sulfates Biological Transport General Chemistry Biosynthetic Pathways 0104 chemical sciences 030104 developmental biology chemistry Biochemistry Fermentation Drug delivery Sulfotransferases Oxidoreductases Metabolic engineering |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-21692-5 |
| Popis: | 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. Chondroitin sulfate (CS) is a type of sulfated glycosaminoglycan that is manufactured by extraction from animal tissues for the treatment of osteoarthritis and in drug delivery applications. Here, the authors report the development of single microbial cell factories capable of compete, one-step biosynthesis of animal-free CS production in E. coli. |
| Databáze: | OpenAIRE |
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