Rational design of microbial strains for novel biochemical products
Natural Sciences and Engineering Research Council of Canada
- Grant type: Strategic Projects - Group
- Years: 2010/11 to 2012/13
- Total Funding: $438,000
University of Toronto
University of Toronto
Increased volatility in the petrochemical feedstocks has necessitated a paradigm shift towards the use of biomass based feedstocks for the synthesis of transportation fuels. In contrast, there have been very few instances of microbial strain engineering for large-scale commodity chemicals with the exception of 1,3 propanediol (DuPont), lactic acid (Cargill), and 1,4 butanediol (Genomatica). A common feature among all of these chemicals is that they are derived primarily from central metabolism. The success of these efforts clearly motivates the microbial strain engineering efforts for other chemicals which are further removed from central metabolism. These include dicarboxylic acids such as succinic, malic, fumaric, itaconic and adipic acids as well as levulinic acid. However, for chemicals such as adipic acid, the synthesis pathways are not present in typical industrial hosts resulting in an additional challenge for strain engineering. Consequently, the objective of this research program is to develop microbial strains that overproduce common chemicals such as malic and fumaric acids as well as chemicals not found in microbial metabolic pathways such as adipic acid in S. cerevisiae. This goal will be accomplished through the following steps, 1) the computational identification of genes whose expression has to be modified as well as genes that need to be incorporated into the host, 2) enzyme screening step to identify the optimal candidate enzymes followed by experimental implementation of the strain designs and 3) comprehensive metabolic characterization of growth physiology and by-product secretion patterns as well as the metabolic flux distribution through C13 isotope labeling. The successful completion of these aims will lead to the development of microbial strains that can overproduce complex chemicals from biomass based feedstocks and lead to sustainable bioprocesses for a variety of industrial chemicals.