Genome-scale model development and genomic sequencing of the oleaginous clade Lipomyces

• Published in: Frontiers in bioengineering and biotechnology Vol. 12; p. 1356551
• Main Authors: Czajka, Jeffrey J, Han, Yichao, Kim, Joonhoon, Mondo, Stephen J, Hofstad, Beth A, Robles, AnaLaura, Haridas, Sajeet, Riley, Robert, LaButti, Kurt, Pangilinan, Jasmyn, Andreopoulos, William, Lipzen, Anna, Yan, Juying, Wang, Mei, Ng, Vivian, Grigoriev, Igor V, Spatafora, Joseph W, Magnuson, Jon K, Baker, Scott E, Pomraning, Kyle R
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.04.2024
• Subjects: BASIC BIOLOGICAL SCIENCES; Bioengineering and Biotechnology; flux balance analysis; genome scale modeling; genome sequencing; genome-scale metabolic model; Lipomyces; oleaginous yeasts; Lipomyces; genome sequencing; oleaginous yeasts; flux balance analysis; genome-scale metabolic model
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2024.1356551

The clade contains oleaginous yeast species with advantageous metabolic features for biochemical and biofuel production. Limited knowledge about the metabolic networks of the species and limited tools for genetic engineering have led to a relatively small amount of research on the microbes. Here, a genome-scale metabolic model (GSM) of NRRL Y-11557 was built using orthologous protein mappings to model yeast species. Phenotypic growth assays were used to validate the GSM (66% accuracy) and indicated that NRRL Y-11557 utilized diverse carbohydrates but had more limited catabolism of organic acids. The final GSM contained 2,193 reactions, 1,909 metabolites, and 996 genes and was thus named iLst996. The model contained 96 of the annotated carbohydrate-active enzymes. iLst996 predicted a flux distribution in line with oleaginous yeast measurements and was utilized to predict theoretical lipid yields. Twenty-five other yeasts in the clade were then genome sequenced and annotated. Sixteen of the species had orthologs for more than 97% of the iLst996 genes, demonstrating the usefulness of iLst996 as a broad GSM for metabolism. Pathways that diverged from iLst996 mainly revolved around alternate carbon metabolism, with ortholog groups excluding NRRL Y-11557 annotated to be involved in transport, glycerolipid, and starch metabolism, among others. Overall, this study provides a useful modeling tool and data for analyzing and understanding species metabolism and will assist further engineering efforts in .