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

Front Bioeng Biotechnol. 2024 Apr 4:12:1356551. doi: 10.3389/fbioe.2024.1356551. eCollection 2024.


The Lipomyces 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 Lipomyces starkeyi 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 Lipomyces clade were then genome sequenced and annotated. Sixteen of the Lipomyces species had orthologs for more than 97% of the iLst996 genes, demonstrating the usefulness of iLst996 as a broad GSM for Lipomyces 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 Lipomyces species metabolism and will assist further engineering efforts in Lipomyces.

Keywords: Lipomyces; flux balance analysis; genome sequencing; genome-scale metabolic model; oleaginous yeasts.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The research was supported by the US Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), Bioenergy Technologies Office (BETO), under Award No. DE-NL0030038. Funding was provided by the US DOE Office of Energy Efficiency and Renewable Energy Bioenergy Technologies Office (BETO) for the Agile BioFoundry. This work (proposal: conducted by the US Department of Energy Joint Genome Institute (, a DOE Office of Science User Facility, was supported by the Office of Science of the US Department of Energy operated under Contract No. DE-AC02-05CH11231. A portion of this work was part of the DOE Joint BioEnergy Institute ( supported by the US Department of Energy, Office of Science, Office of Biological and Environmental Research, through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the US Department of Energy. The genome of Myxozyma melibiosi Phaff 52-87 was sequenced and annotated as part of the 1000 Fungal Genomes Project (proposal: 10.46936/10.25585/60001019). JJC is grateful for support from a Linus Pauling Distinguished Fellowship by PNNL-Laboratory Directed Research and Development Program. Pacific Northwest National Laboratory is a multi-program national laboratory operated for the US Department of Energy by Battelle Memorial Institute under contract DE-AC05-76RL01830.