How do engineered Yarrowia lipolytica strains secrete free fatty acids: hints from comparative transcriptomics.
| Autor: | Salvador López JM; Centre for Synthetic Biology, Ghent University,Coupure Links 653, 9000 Gent, Belgium., Vidal L; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Domaine de Vilvert, 78350 Jouy-en-Josas, France., Adiutama MP; Centre for Synthetic Biology, Ghent University,Coupure Links 653, 9000 Gent, Belgium., Van Nieuwerburgh F; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460 9000 Gent, Belgium., Deforce D; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460 9000 Gent, Belgium., Nicaud JM; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Domaine de Vilvert, 78350 Jouy-en-Josas, France., Van Bogaert INA; Centre for Synthetic Biology, Ghent University,Coupure Links 653, 9000 Gent, Belgium. |
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| Jazyk: | angličtina |
| Zdroj: | FEMS yeast research [FEMS Yeast Res] 2023 Jan 04; Vol. 23. |
| DOI: | 10.1093/femsyr/foad027 |
| Abstrakt: | Yarrowia lipolytica has been considered one of the most promising platforms for the microbial production of fatty acids and derived products. The deletion of the faa1 gene coding for an acyl-CoA synthetase leads to the accumulation and secretion of free fatty acids (FFAs) into the extracellular space. The secretion of products is beneficial for the development of microbial cell factories to avoid intracellular inhibitory effects and reduce downstream processing costs. However, the mechanism behind the secretion of fatty acids is not well known. As a starting point, we compared the transcriptome of this mutant showing FFA secretion to a wildtype-like strain not showing this phenotype. The 12 most upregulated genes were evaluated for involvement in FFA secretion by the creation of deletion and overexpression mutants, among them MCH2, YMOH, three cell wall proteins CWP3, CWP4, and CWP11, M12B, and three proteins with unknown functions YUP1, YUP2, and YUP3. None of these proteins take a clear or isolated role in FFA export. As the transcriptomic data revealed an overrepresentation of cell wall-related proteins, some of them were further examined on a theoretical and experimental way. Surprisingly, overexpression of Ygpi led to the production of FFAs in the wildtype-like genetic background. Finally, some of the evaluated genes showed involvement in resistance to FFA toxicity. (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.) |
| Databáze: | MEDLINE |
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