Production of toxic chemical based on a mathematical model and metabolic flux optimization

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So Young Choi, Hyegwon Park, Dokyun Na, and Sang Yup Lee

Korea Advanced Institute of Science and Technology, South Korea

Production of target chemical compounds in large quantity is achieved through a number of metabolic engineering strategies. For high production of target chemicals, it is generally required to supply enough precursor pool by redirection of metabolic fluxes. When the goal is overproduction of target chemical which has toxicity, fine-tuning of metabolic flux is needed because highly accumulated intermediate and its efficient conversion to the toxic target may induce cell death or severe growth retardation, leading to decreased target production. For toxic chemical production, concentration of intermediates should be well-balanced to produce toxic chemical as high as host cell can tolerate. Here, to produce phenol, a toxic chemical in Escherichia coli, we developed a mathematical model through tyrosine biosynthetic pathway as a model. The model-based control of tyrosine production fosters to find the maximal phenol production in Escherichia coli. The suitable control of intermediate concentration in assistance with a math model gives an insight to the metabolic engineering for toxic chemical compounds production. [“This work was supported by Intelligent Synthetic Biology Center (2011-0031963) of Korea through the Global Frontier Research Program of the Ministry of Education, Science and Technology (MEST).”]