With rising concerns about sustainable practices, environmental complications, and declining resources, metabolic engineers are transforming microorganisms into cellular factories for producing capsular polysaccharides (CPSs). This review provides an overview of strategies employed for the metabolic engineering of heparosan, chondroitin, hyaluronan, and polysialic acid — four CPSs that are of interest for manufacturing a variety of biomedical applications. Methods described include the exploitation of wild-type and engineered native CPS producers, as well as genetically engineered heterologous hosts developed through the improvement of naturally existing pathways or newly (de novo) designed ones. The implementation of methodologies like gene knockout, promoter engineering, and gene expression level control has resulted in multiple-fold improvements in CPS fermentation titers compared with wild-type strains, and substantial increases in productivity, reaching as high as 100% in some cases. Optimization of these biotechnological processes can permit the adoption of industrially competitive engineered microorganisms to replace traditional sources that are generally toxic, unreliable, and inconsistent in product quality.
The lack of availability of glycans and glycoconjugates has severely limited the development of the field of glycobiology. This issue of Emerging Topics in Life Sciences features nine reviews by respected scientists in the field and deals with the application of metabolic engineering to the production of these complex carbohydrate or saccharide structures. The cover image illustrates that capsular polysaccharides and other bioengineered compounds can be generated by engineered cells, such as Escherichia coli, through the application of various metabolic engineering tools and strategies. The image was kindly provided by Robert J. Linhardt (Rensselaer Polytechnic Institute) and designed by Asher Williams (Rensselaer Polytechnic Institute).
Metabolic engineering of capsular polysaccharides
Mattheos A.G. Koffas, Robert J. Linhardt, Asher Williams, Robert J. Linhardt, Mattheos A.G. Koffas; Metabolic engineering of capsular polysaccharides. Emerg Top Life Sci 26 October 2018; 2 (3): 337–348. doi: https://doi.org/10.1042/ETLS20180003
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