Complete biosynthesis of a sulfated chondroitin in Escherichia coli.

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. 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.
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