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

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.

doi:10.3389/fbioe.2024.1356551

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

Journal Article · Thu Apr 04 00:00:00 EDT 2024 · Frontiers in Bioengineering and Biotechnology

DOI:https://doi.org/10.3389/fbioe.2024.1356551· OSTI ID:2335760

Czajka, Jeffrey J. ^[1]; Han, Yichao ^[1]; ^[2]; Mondo, Stephen J. ^[3]; Hofstad, Beth A. ^[1]; Robles, AnaLaura ^[1]; Haridas, Sajeet ^[4]; Riley, Robert ^[4]; LaButti, Kurt ^[4]; Pangilinan, Jasmyn ^[4]; Andreopoulos, William ^[4]; Lipzen, Anna ^[4]; Yan, Juying ^[4]; Wang, Mei ^[4]; Ng, Vivian ^[4]; Grigoriev, Igor V. ^[5]; Spatafora, Joseph W. ^[6]; ^[2]; ^[7]; ^[1]

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); USDOE Agile BioFoundry, Emeryville, CA (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); USDOE Agile BioFoundry, Emeryville, CA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States)
USDOE Joint Genome Institute (JGI), Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Colorado State Univ., Fort Collins, CO (United States)
USDOE Joint Genome Institute (JGI), Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
USDOE Joint Genome Institute (JGI), Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Oregon State Univ., Corvallis, OR (United States)
USDOE Agile BioFoundry, Emeryville, CA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); USDOE Joint Genome Institute (JGI), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Joint Genome Institute; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation. Bioenergy Technologies Office (BETO); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; AC05-76RL01830

OSTI ID:: 2335760

Report Number(s):: PNNL-SA--193362

Journal Information:: Frontiers in Bioengineering and Biotechnology, Journal Name: Frontiers in Bioengineering and Biotechnology Vol. 12; ISSN 2296-4185

Publisher:: Frontiers Media S.A.Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Lipomyces
flux balance analysis
genome scale modeling
genome sequencing
genome-scale metabolic model
oleaginous yeasts

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

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