Pereira, Filipa published the artcileModel-guided development of an evolutionarily stable yeast chassis, Quality Control of 97-67-6, the main research area is transcriptome proteome metabolome succinate fumarate malate dehydrogenase Saccharomyces; adaptive laboratory evolution; chassis cell; metabolic engineering; multi-objective optimization; systems biology.
First-principle metabolic modeling holds potential for designing microbial chassis that are resilient against phenotype reversal due to adaptive mutations. Yet, the theory of model-based chassis design has rarely been put to rigorous exptl. test. Here, we report the development of Saccharomyces cerevisiae chassis strains for dicarboxylic acid production using genome-scale metabolic modeling. The chassis strains, albeit geared for higher flux towards succinate, fumarate and malate, do not appreciably secrete these metabolites. As predicted by the model, introducing product-specific TCA cycle disruptions resulted in the secretion of the corresponding acid. Adaptive laboratory evolution further improved production of succinate and fumarate, demonstrating the evolutionary robustness of the engineered cells. In the case of malate, multi-omics anal. revealed a flux bypass at peroxisomal malate dehydrogenase that was missing in the yeast metabolic model. In all three cases, flux balance anal. integrating transcriptomics, proteomics and metabolomics data confirmed the flux re-routing predicted by the model. Taken together, our modeling and exptl. results have implications for the computer-aided design of microbial cell factories.
Molecular Systems Biology published new progress about Metabolome. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Quality Control of 97-67-6.
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