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Engineering Static and Dynamic Tuning of Malonyl-CoA Derived Metabolite Biosynthesis in Microorganisms
(Seminar/Conference)
Dr. Mattheos Koffas
Associate Professor
Department of Chemical & Biological Engineering
Rensselaer Polytechnic Institute
Abstract
Our research goal is to utilize the richness, versatility but also simplicity of microbial organisms in order to make them ideally suited to convert renewable carbon resources into chemicals. For the purpose of reprogramming the cellular network, we have developed an in silico model of the genome-wide metabolism of Escherichia coli. Through the application of Metabolic Flux Analysis, we predicted genetic modifications that lead to dramatic increases in production levels. Such Systems Biology approaches, in combination with traditional genetic engineering have resulted in robust production levels and commercially viable processes for the synthesis of important molecules, in particular ones that derive from malonyl-CoA. We also report the engineering of feedback controls for dynamic tuning of metabolic fluxes in E. coli. Specifically, we have identified a dual transcriptional regulator that can act either as an activator or a repressor for two different promoters. The level of activation or repression is dependent on the level of intracellular malonyl-CoA. By engineering this synthetic malonyl-CoA controller, we were able to dynamically control the expression of a malonyl-CoA source pathway and a malonyl-CoA sink pathway. This dynamic control efficiently redirected the carbon flux through malonyl-CoA to allow the high yield production of free fatty acids in E. coli.
Biography
Dr. Mattheos Koffas is an associate professor in the department of Chemical and Biological Engineering at Rensselaer Polytechnic Institute and also the Career Development Associate Professor of the Biocatalysis Constellation at RPI since 2011. He received his PhD from MIT in 2001. He was a Visiting Research Scientist at DuPont Central Research from 2001 to 2002. Dr. Koffas works in the field of metabolic engineering and systems biotechnology. He currently serves on the editorial board of several journals, including the Current Opinion in Biotechnology, BMC Plant Biology, Metabolic Engineering Communications and Biotechnology and Bioprocess Engineering. He has published more than 50 peer review papers and holds a number of patents some of which have been commercialized.
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(540) 231-0680