464684 Overcoming Metabolic Toxicity for Improved Isoprenoid Production

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Steven Edgar, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA and Gregory Stephanopoulos, Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA

Isoprenoids are a large class of secondary metabolites with more than 55,000 currently known, many of which have important industrial roles. While two pathways exist for the production of these compounds, the relatively-newly discovered microbial methylerythritol phosphate (MEP) pathway has failed to produce comparable results to the more extensively studied MVA pathway. However, the MEP pathway has distinct advantages including higher theoretical yield, and a redox balance that enables anaerobic production. Here we discuss a methodology to improve isoprenoid pathway production through the MEP pathway. We target toxicity of intermediate metabolites as a key factor limiting MEP pathway flux. We then probe knockout strains and evaluate their effect on cell health, growth rate, and MEP-pathway flux; arriving at an optimized microbial chassis which will enable future work on the MEP pathway.

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