@article{2609, author = {Hoang Dinh V and Patrick Suthers and Siu Chan and Yihui Shen and Tianxia Xiao and Anshu Deewan and Sujit Jagtap and Huimin Zhao and Christopher Rao V and Joshua Rabinowitz and Costas Maranas}, title = {A comprehensive genome-scale model for IFO0880 accounting for functional genomics and phenotypic data.}, abstract = {
is a red, basidiomycetes yeast that can accumulate a large amount of lipids and produce carotenoids. To better assess this non-model yeast\&$\#$39;s metabolic capabilities, we reconstructed a genome-scale model of IFO0880\&$\#$39;s metabolic network (1108) accounting for 2204 reactions, 1985 metabolites and 1108 genes. In this work, we integrated and supplemented the current knowledge with in-house generated biomass composition and experimental measurements pertaining to the organism\&$\#$39;s metabolic capabilities. Predictions of genotype-phenotype relations were improved through manual curation of gene-protein-reaction rules for 543 reactions leading to correct recapitulations of 84.5\% of gene essentiality data (sensitivity of 94.3\% and specificity of 53.8\%). Organism-specific macromolecular composition and ATP maintenance requirements were experimentally measured for two separate growth conditions: (i) carbon and (ii) nitrogen limitations. Overall, 1108 reproduced \&$\#$39;s utilization capabilities for 18 alternate substrates, matched measured wild-type growth yield, and recapitulated the viability of 772 out of 819 deletion mutants. As a demonstration to the model\&$\#$39;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.
}, year = {2019}, journal = {Metab Eng Commun}, volume = {9}, pages = {e00101}, month = {12/2019}, issn = {2214-0301}, doi = {10.1016/j.mec.2019.e00101}, language = {eng}, }