Insights into optimization of oleaginous fungi - genome-scale metabolic reconstruction and analysis of Umbelopsis sp. WA50703

Oleaginous fungi, known for their high lipid content--up to 80% of their dry mass--are of significant interest for biotechnological applications, particularly in biofuel and fatty acid production. Among these, the genus Umbelopsis, a common soil saprotroph of the Mucoromycota phylum, stands out for its rapid growth, low nutritional requirements, and ability to produce substantial amounts of lipids, especially polyunsaturated fatty acids (PUFAs). Despite previous studies on lipid production in Umbelopsis, metabolic engineering has been underexplored. This study fills that gap by presenting the first comprehensive metabolic model for Umbelopsis sp. WA50703, encompassing 2413 metabolites, 2216 reactions, and 1629 genes (iMD1629). The model demonstrated strong predictive accuracy, correctly predicting metabolic capabilities in 82.1% of cases when evaluated against experimental data. Using the Flux Scanning based on Enforced Objective Flux (FSEOF) algorithm, the study identified 33 genes linked to 23 metabolic reactions. Notably, reactions catalysed by acetyl-CoA carboxylase and carbonic anhydrase emerged as prime candidates for up-regulation. These findings provide a solid framework for future metabolic engineering efforts to optimize PUFA production in Umbelopsis strains. ImportanceUmbelopsis strains are capable of producing valuable compounds like polyunsaturated fatty acids (PUFAs). These compounds are essential for human health, found in various foods and supplements that support heart and brain function. In this study we developed a computer model to better understand how this fungus works at a metabolic level, guiding further research investigations towards optimization of PUFAs production in a cost-effective way. This research lays the groundwork for future innovations in metabolic engineering of Umbelopsis PUFA production leading to healthier food options and a more sustainable food system, directly impacting everyday life.