20.500.12556/DiRROS-24229 Transcriptomics‑based analysis of acetate and propionate transport and metabolism in Yarrowia lipolytica Background. Yarrowia lipolytica is a promising host for sustainable microbial oil production from waste-derived carboxylic acids such as acetate and propionate. Nonetheless, the molecular mechanisms underlying the metabolism and assimilation of these substrates, particularly under nitrogen limitation, are still not fully understood. Results. We conducted a multi-condition transcriptomic analysis of Y. lipolytica strain EXF-17398 under nitrogen-limiting conditions to investigate its transcriptional adaptation to acetate and propionate utilisation. Our results revealed distinct transcriptional responses associated with metabolic adaptation, including the coordinated regulation of Jen and Gpr carboxylate transporter families, suggesting a dual system for carboxylate uptake. JEN5 and GPR1 appear central to propionate and acetate utilisation, respectively. Our data suggest that propionate toxicity is mitigated through its conversion via the methylcitrate cycle and potentially the malonate semialdehyde pathway, preventing accumulation of cytotoxic propionyl-CoA in the cytosol. The upregulation of carnitine acyltransferases suggests active mitochondrial transport of acyl-CoAs, linking detoxification with energy metabolism. Under tested conditions, the de novo lipid synthesis was consistent with carbon overflow from acetyl-CoA and propionyl-CoA, supported by intracellular nitrogen recycling and redox balancing, independent of classical nitrogen regulatory pathways. Conclusions. These findings illustrate the capacity of Y. lipolytica to coordinate carbon and nitrogen metabolism during carboxylate utilisation, such as acetate and propionate, offering insights to guide the optimisation of microbial oil production from renewable feedstocks. propionate transport metabolism propionati prenos metabolizem Yarrowia lipolytica true false true Springer Nature Švica Angleški jezik Slovenski jezik © The Author(s) 2025. Neznano 2025-11-21 13:34:28 2025-11-21 13:34:28 2025-11-22 03:57:12 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Soavtorji iz Slovenije: Urška Hancman, Neža Čadež, Cene Gostinčar, Uroš Petrovič; Opis vira z dne 13. 11. 2025; str. 1-17 Vol. 18, article no. 112 10 Nov. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2025-06-17 2025-10-19 2025-11-10 57 2731-3654 10.1186/s13068-025-02713-7 257066755 https://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-025-02713-7 1 6e9a347c-c6d6-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36081 RAZ_Zganjar_Mia_2025.pdf RAZ_Zganjar_Mia_2025.pdf The assembled genome and raw expression data have been deposited at GeneBank under the BioProject accession number [PRJNA955139](https:/www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA955139). 1 FEE120542D7E2F2923F94C33CD218BE5 3786ef05feae28a9540f65c2e0c0ebd20753b0ae01120f0b84e79fe2f941b9b6 87246adc-c6d6-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36082 Institut Jožef Stefan 0 0 0