Heparan sulfate (HS) is a glycosaminoglycan produced by all mammalian cells that plays important roles in physiology and various pathologies. Heparin is a highly sulfated form of HS that is used clinically as an anticoagulant. Heparin and HSs may also have therapeutic benefits for a wide variety of other indications. Cultured mammalian cells produce HS and, through genetic modification, have been used to elucidate the biosynthetic pathway. Recently, metabolic engineering has been used to produce HS from cultured mammalian cells for clinical purposes. This review describes the HS biosynthetic pathway and its manipulation through metabolic engineering to produce bioengineered HSs. We also discuss current challenges and opportunities to advance the field of HS metabolic engineering.
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Cover Image
Cover Image
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 mammalian cells to produce heparan sulfates
Mattheos A.G. Koffas, Robert J. Linhardt, Bryan E. Thacker, Susan T. Sharfstein; Metabolic engineering of mammalian cells to produce heparan sulfates. Emerg Top Life Sci 26 October 2018; 2 (3): 443–452. doi: https://doi.org/10.1042/ETLS20180007
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