A genomics approach for improving production of Itaconic Acid by Aspergillus terreus

Itaconic acid is an unsaturated dicarboxylic acid produced industrially by fermentative processes using the fungus Aspergillus terreus (1,2). It is in widespread use around the world as a building block compound for polymer production, and can be used widely as a sustainable replacement for petroleum-derived acrylic and methacrylic acids (2). While global use and production of itaconic acid are already very high at 30 and 50 kt a year, respectively, itaconic acid is still too expensive to compete directly with petroleum derivatives for many applications (1). As a result, great interest exists in lowering the costs of production through process-based methods or genetic improvement of the strains of fungus that secrete it. While these efforts have to some extent been successful, further improvement is required to lower costs below that of petroleum. We have instituted a new approach involving three gene targets identified from transcriptomic analysis of a related fungus, Aspergillus niger. Industrially A. niger is used for the production of citric acid, a direct precursor of itaconic acid. In a high-producing strain of A. niger three transcription factors are significantly downregulated relative to the wildtype strain. Our approach centers on using Cas9-based methods to induce inactivating double-stranded DNA breaks in the corresponding three genes in Aspergillus terreus. Our end goal is to produce a novel strain of A. terreus which produces greater yields of itaconic acid in a shorter period of time.

References:

1. Steiger, Matthias Georg, et al. "Biochemistry of microbial itaconic acid production." Frontiers in microbiology 4 (2013): 23.
2. Willke, Th, and K-D. Vorlop. "Biotechnological production of itaconic acid." Applied Microbiology and Biotechnology 56.3 (2001): 289-295.