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Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow

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Abstract

Glycosaminoglycans [GAGs] are essential heteropolysaccharides in vertebrate tissues that are also, in certain cases, employed as virulence factors by microbes. Hyaluronan [HA], heparin, and chondroitin sulfate [CS] are GAGs currently used in various medical applications and together are multi-billion dollar products thus targets for production by animal-free manufacture. By using bacteria as the source of GAGs, the pathogen’s sword may be converted into a plowshare to help avoid potential liabilities springing from the use of animal-derived GAGs including adventitious agents (e.g., prions, pathogens), antigenicity, degradation of the environment, and depletion of endangered species. HA from microbes, which have a chemical structure identical to human HA, has already been commercialized and sold at the ton-scale. Substantial progress towards microbial heparin and CS has been made, but these vertebrate polymers are more complicated structurally than the unsulfated bacterial polysaccharide precursors thus require additional processing steps. This review provides an overview of GAG structure, medical applications, microbial biosynthesis, and the state of bacterial GAG production systems. Representatives of all glycosyltransferase enzymes that polymerize the sugar chains of the three main GAGs have been identified and serve as the core technology to harness, but the proteins involved in sugar precursor formation and chain export steps of biosynthesis are also essential to the GAG production process. In addition, this review discusses future directions and potential important issues. Overall, this area is poised to make great headway to produce safer (both increased purity and more secure supply chains) non-animal GAG-based therapeutics.

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Acknowledgments

I would like to thank the many colleagues and students who have helped explore this exciting area over the last two decades. I also thank funding agencies including the Oklahoma Center for Advancement of Science and Technology (OCAST), the National Science Foundation, and the National Institutes of Health for past support.

Conflict of interest

The author is Chief Scientist of 4 biotechnology companies (Hyalose, Choncept, Heparinex, and Caisson Biotech) commercializing GAG production, but no corporate funding was used to support this review.

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  1. Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73126, USA

    Paul L. DeAngelis

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DeAngelis, P.L. Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow. Appl Microbiol Biotechnol 94, 295–305 (2012). https://doi.org/10.1007/s00253-011-3801-6

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