A comprehensive genome-scale model for IFO0880 accounting for functional genomics and phenotypic data.

Publication Year
2019

Type

Journal Article
Abstract

is a red, basidiomycetes yeast that can accumulate a large amount of lipids and produce carotenoids. To better assess this non-model yeast's metabolic capabilities, we reconstructed a genome-scale model of IFO0880's metabolic network (1108) accounting for 2204 reactions, 1985 metabolites and 1108 genes. In this work, we integrated and supplemented the current knowledge with in-house generated biomass composition and experimental measurements pertaining to the organism's metabolic capabilities. Predictions of genotype-phenotype relations were improved through manual curation of gene-protein-reaction rules for 543 reactions leading to correct recapitulations of 84.5% of gene essentiality data (sensitivity of 94.3% and specificity of 53.8%). Organism-specific macromolecular composition and ATP maintenance requirements were experimentally measured for two separate growth conditions: (i) carbon and (ii) nitrogen limitations. Overall, 1108 reproduced 's utilization capabilities for 18 alternate substrates, matched measured wild-type growth yield, and recapitulated the viability of 772 out of 819 deletion mutants. As a demonstration to the model's fidelity in guiding engineering interventions, the OptForce procedure was applied on 1108 for triacylglycerol overproduction. Suggested interventions recapitulated many of the previous successful implementations of genetic modifications and put forth a few new ones.

Journal
Metab Eng Commun
Volume
9
Pages
e00101
Date Published
2019 Dec
ISSN Number
2214-0301
Alternate Journal
Metab Eng Commun
PMCID
PMC6838544
PMID
31720216