Sunday, July 26, 2009
P99

Dynamic metabolic engineering strategy to improve productivity of bioprocesses

Nikolaos Anesiadis, William R. Cluett, and Radhakrishnan Mahadevan. Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada

Recently, there has been renewed interest in the use of biological processes for the synthesis of biochemicals rather than traditional petrochemical processes. This has motivated the development of novel strategies to improve the efficiency of these bioprocesses by increasing the product yield, titer and the productivity through metabolic engineering. However, in several cases when genes are deleted to increase the yield of a desired product, a decreased growth rate is observed, which strongly affects the productivity. In such cases, one of the strategies that can enhance productivity is the dynamic expression of the genes that have to be knocked out, to promote growth initially. In order to achieve this control strategy, inducible promoters can be used to manipulate the gene expression dynamically. However, the use of inducers in commercial applications may not be feasible due to their high cost.

With the emergence of synthetic biology, the concept of controlling a specific pathway of a metabolic network in a predefined and programmable fashion comes closer to reality. We have recently proposed the use of a genetic controller to manipulate dynamically the expression of target genes through the use of an integrated quorum sensing and toggle switch circuit. This will be beneficial for high-volume bioproducts where gene deletions cause a large growth impairment and significantly decrease the batch time of a bioprocess. Here, we explore the effect of parameters of the circuit on the dynamics and the productivity of succinate production in E. coli strain MG1655.