A group around Shuying GU and Jingen LI at CAS Tianjin Institute of Industrial Biotechnology has engineered Myceliophthora thermophila using the CRISPR/Cas9 system. They introduced fumarase of Candidakrusei fumarase into M. thermophila and disrupted the intracellular fumarate digestion pathway by deletion of the two fumarate reductase and the mitochondrial fumarase genes of M. thermophila. Increasing the pool size of malate, the precursor of fumaric acid, significantly increased the final fumaric acid titer. Finally, disruption of the malate–aspartate shuttle increased the intracellular malate content. The final strain could produce up to 17 g/L fumaric acid from glucose in a fed-batch fermentation process.
CAS news release, February 22, 2019
