The road to animal-free glycosaminoglycan production: current efforts and bottlenecks

[Display omitted] •Animal extraction is monopolizing the glycosaminoglycan (GAG) production industry.•Focus on synthetic GAGs using chemical, chemoenzymatic and biosynthesis methods.•Alternate production approaches cannot yet meet worldwide demands.•Bottlenecks discussed include intracellular precursors and enzyme engineering. Animal-extraction, despite its limitations, continues to monopolize the fast-growing glycosaminoglycan (GAG) industry. The past few years have seen an increased interest in the development of alternative GAG production methods. Chemical and chemo-enzymatic synthesis and biosynthesis from GAG producing cells, including engineered recombinant strains, are currently under investigation. Despite achieving considerable successes, these alternate approaches cannot yet meet worldwide demands for these important polysaccharides. Bottlenecks associated with achieving high-titers need to be addressed using newly developed tools. Several parameters including chassis choice, analytics, intracellular precursor synthesis, enzyme engineering and use of synthetic biology tools need to be optimized. We envision that new engineering approaches together with advances in the basic biology and chemistry of GAGs will move GAG production beyond its currently limited supply chain.