Genome Scale Metabolic Model Assisted Strain Designs for Itaconic Acid Production in Yeast

Itaconic acid production by the natural producer Aspergillus terreus could be limited by difficult fermentation characteristics, such as high viscosity, shear stress, and low growth rate. An alternative host, such as Saccharomyces cerevisiae, might open new revenue for further process intensification. Various pathways for itaconic acid production in yeast, varying in the supply of AcCoA precursor, were designed using a genome scale metabolic model. By comparing the flux distribution between optimal growth and optimal production, additional targets were identified for overexpression and deletion. Four pathway variants were selected for ‘build’ and ‘test’. The best tested variant was further improved in several iterative rounds using Design of Experiment methodologies. The full design-build-test-learn cycle delivered the highest itaconic acid titer in S. cerevisiae to date.