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Heparin and related polysaccharides: synthesis using recombinant enzymes and metabolic engineering

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Abstract

Glycosaminoglycans are linear anionic polysaccharides that exhibit a number of important biological and pharmacological activities. The two most prominent members of this class of polysaccharides are heparin/heparan sulfate and the chondroitin sulfates (including dermatan sulfate). These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of most animal cells. The chemical synthesis of these glycosaminoglycans is precluded by their structural complexity. Today, we depend on food animal tissues for their isolation and commercial production. Ton quantities of these glycosaminoglycans are used annually as pharmaceuticals and nutraceuticals. The variability of animal-sourced glycosaminoglycans, their inherent impurities, the limited availability of source tissues, the poor control of these source materials, and their manufacturing processes suggest a need for new approaches for their production. Over the past decade, there have been major efforts in the biotechnological production of these glycosaminoglycans. This mini-review focuses on the use of recombinant enzymes and metabolic engineering for the production of heparin and chondroitin sulfates.

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Acknowledgments

The authors are grateful for support from the National Institutes of Health (HL094463, GM102137, HL62244, HL096972) and the National Science Foundation (MCB-1448657).

Conflict of interest

The authors declare no competing interests.

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Authors and Affiliations

  1. Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 121806, USA

    Matthew Suflita, Mattheos Koffas & Robert J. Linhardt

  2. Department of Chemistry and Chemical, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 121806, USA

    Li Fu & Robert J. Linhardt

  3. Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 121806, USA

    Wenqin He, Mattheos Koffas & Robert J. Linhardt

  4. Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 121806, USA

    Robert J. Linhardt

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  1. Matthew Suflita
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Correspondence to Robert J. Linhardt.

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Suflita, M., Fu, L., He, W. et al. Heparin and related polysaccharides: synthesis using recombinant enzymes and metabolic engineering. Appl Microbiol Biotechnol 99, 7465–7479 (2015). https://doi.org/10.1007/s00253-015-6821-9

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  • DOI: https://doi.org/10.1007/s00253-015-6821-9

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