Large-scale production of plant secondary metabolites is of interest because of their application in production of many valuable products. Recent advances in the area of DNA recombinant technology has made it possible to produce these valuable compounds using microbial routes. The objective of this work was, to design a platform strain of Saccharomyces cerevisiae with improved intracellular tyrosine pools using computational modeling. This engineered yeast could be used as a host for producing important plant secondary metabolites on an industrial-scale. In this study, a combination of steady-state and dynamic modeling methods were used for strain design. Initial strain design was performed using steady-state modeling, and the predictions from steady-state modeling were prioritized for experimental validation using dynamic modeling. The final strategy proposed included deletion of PDC1, ZWF1, ARO10; over-expression of ALD6, and alleviation of tyrosine feedback resistance in shikimate pathway. Initial experiments for validation of this strategy showed promising results.

Large-scale production of plant secondary metabolites is of interest because of their application in production of many valuable products. Recent advances in the area of DNA recombinant technology has made it possible to produce these valuable compounds using microbial routes. The objective of this work was, to design a platform strain of Saccharomyces cerevisiae with improved intracellular tyrosine pools using computational modeling. This engineered yeast could be used as a host for producing important plant secondary metabolites on an industrial-scale. In this study, a combination of steady-state and dynamic modeling methods were used for strain design. Initial strain design was performed using steady-state modeling, and the predictions from steady-state modeling were prioritized for experimental validation using dynamic modeling. The final strategy proposed included deletion of PDC1, ZWF1, ARO10; over-expression of ALD6, and alleviation of tyrosine feedback resistance in shikimate pathway. Initial experiments for validation of this strategy showed promising results.