Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

In Silico Design of Saccharomyces cerevisiae Strains for Improved Production of Chondroitin

Version 1 : Received: 19 December 2023 / Approved: 20 December 2023 / Online: 20 December 2023 (10:56:42 CET)
Version 2 : Received: 15 January 2024 / Approved: 16 January 2024 / Online: 16 January 2024 (09:58:41 CET)

How to cite: Couto, M. R.; Rodrigues, J. L.; Dias, O.; Rodrigues, L. R. In Silico Design of Saccharomyces cerevisiae Strains for Improved Production of Chondroitin. Preprints 2023, 2023121479. https://doi.org/10.20944/preprints202312.1479.v1 Couto, M. R.; Rodrigues, J. L.; Dias, O.; Rodrigues, L. R. In Silico Design of Saccharomyces cerevisiae Strains for Improved Production of Chondroitin. Preprints 2023, 2023121479. https://doi.org/10.20944/preprints202312.1479.v1

Abstract

Chondroitin sulfate is a glycosaminoglycan that has gained widespread use in nutraceuticals and pharmaceuticals, mainly for treating osteoarthritis. Traditionally, it has been extracted from animal cartilage but recently, biotechnological processes have emerged as a commercial alternative to avoid the risk of viral or prion contamination and offer a vegan-friendly source. Typically, these methods involve producing the chondroitin backbone using pathogenic bacteria and then modifying it enzymatically through the action of sulfotransferases. Despite the challenges of expressing active sulfotransferases in bacteria, the use of eukaryotic microorganisms is still limited to a few works using Pichia pastoris. To create a safer and efficient biotechnological platform, we have constructed a biosynthetic pathway for chondroitin production in S. cerevisiae. Furthermore, as genome-scale models are valuable tools for identifying novel targets for metabolic engineering, a stoichiometric model of chondroitin-producing S. cerevisiae has been developed and used in optimization algorithms. Our research has yielded several novel targets, such as uridine diphosphate(UDP)-N-acetylglucosamine pyrophosphorylase (QRI1), glucosamine-6-phosphate acetyltransferase (GNA1) or N-acetylglucosamine-phosphate mutase (PCM1) overexpression that might enhance chondroitin production, which will guide future experimental research to develop more efficient host organisms for the biotechnological production process.

Keywords

chondroitin; Saccharomyces cerevisiae; metabolic models; metabolic engineering

Subject

Biology and Life Sciences, Biology and Biotechnology

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