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Bacterial glycobiotechnology: A biosynthetic route for the production of biopharmaceutical glycans

Paliya, Balwant S; Sharma, Vivek K; Tuohy, Maria G; Singh, Harikesh B; Koffas, Mattheos; Benhida, Rachid; Tiwari, Brijesh K; ... Gupta, Vijai K; + view all (2023) Bacterial glycobiotechnology: A biosynthetic route for the production of biopharmaceutical glycans. Biotechnology Advances , 67 , Article 108180. 10.1016/j.biotechadv.2023.108180. Green open access

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Abstract

The recent advancement in the human glycome and progress in the development of an inclusive network of glycosylation pathways allow the incorporation of suitable machinery for protein modification in non-natural hosts and explore novel opportunities for constructing next-generation tailored glycans and glycoconjugates. Fortunately, the emerging field of bacterial metabolic engineering has enabled the production of tailored biopolymers by harnessing living microbial factories (prokaryotes) as whole-cell biocatalysts. Microbial catalysts offer sophisticated means to develop a variety of valuable polysaccharides in bulk quantities for practical clinical applications. Glycans production through this technique is highly efficient and cost-effective, as it does not involve expensive initial materials. Metabolic glycoengineering primarily focuses on utilizing small metabolite molecules to alter biosynthetic pathways, optimization of cellular processes for glycan and glycoconjugate production, characteristic to a specific organism to produce interest tailored glycans in microbes, using preferably cheap and simple substrate. However, metabolic engineering faces one of the unique challenges, such as the need for an enzyme to catalyze desired substrate conversion when natural native substrates are already present. So, in metabolic engineering, such challenges are evaluated, and different strategies have been developed to overcome them. The generation of glycans and glycoconjugates via metabolic intermediate pathways can still be supported by glycol modeling achieved through metabolic engineering. It is evident that modern glycans engineering requires adoption of improved strain engineering strategies for creating competent glycoprotein expression platforms in bacterial hosts, in the future. These strategies include logically designing and introducing orthogonal glycosylation pathways, identifying metabolic engineering targets at the genome level, and strategically improving pathway performance (for example, through genetic modification of pathway enzymes). Here, we highlight current strategies, applications, and recent progress in metabolic engineering for producing high-value tailored glycans and their applications in biotherapeutics and diagnostics.

Type: Article
Title: Bacterial glycobiotechnology: A biosynthetic route for the production of biopharmaceutical glycans
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biotechadv.2023.108180
Publisher version: https://doi.org/10.1016/j.biotechadv.2023.108180
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Bacteria, Pathway engineering, Engineered glycans, Glycoconjugates, Biopharmaceutical uses
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
URI: https://discovery.ucl.ac.uk/id/eprint/10171190
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