Genome-scale metabolic reconstruction of the non-model yeast Issatchenkia orientalis SD108 and its application to organic acids production

Many platform chemicals can be produced from renewable biomass by microorganisms, with organic acids making up a large fraction. Intolerance to the resulting low pH growth conditions, however, remains a challenge for the industrial production of organic acids by microorganisms. Issatchenkia orientalis SD108 is a promising host for industrial production because it is tolerant to acidic conditions as low as pH 2.0. With the goal to systematically assess the metabolic capabilities of this non-model yeast, we developed a genome-scale metabolic model for I. orientalis SD108 spanning 850 genes, 1826 reactions, and 1702 metabolites. In order to improve the model's quantitative predictions, organism-specific macromolecular composition and ATP maintenance requirements were determined experimentally and implemented. We examined its network topology, including essential genes and flux coupling analysis and drew comparisons with the Yeast 8.3 model for Saccharomyces cerevisiae. We explored the carbon substrate utilization and examined the organism's production potential for the industrially-relevant succinic acid, making use of the OptKnock framework to identify gene knockouts which couple production of the targeted chemical to biomass production. The genome-scale metabolic model iIsor850 is a data-supported curated model which can inform genetic interventions for overproduction.