Global energy and environmental concerns have driven the development of biological production from renewable sources. Fermentation processes utilizing microorganisms such as Escherichia coli and yeast have been developed to produce chemicals from sugar. Recently, improvement in genetic manipulation techniques enables constructing desired metabolic pathways in microorganisms. Through the tools of synthetic biology and metabolic engineering, many microbes have been modified to biologically produce valuable fuels and chemicals which are commonly derived from petroleum. We are focusing on 2-keto acid based biosynthesis pathways. 2-Keto acids, which are key intermediates in amino acid biosynthesis, can be converted to a wide range of chemicals by combination of decarboxylation, reduction, oxidation, chain elongation, and condensation. Various metabolic pathways based on 2-keto acids have been designed and constructed to produce alcohols, aldehydes, acids, and esters, which are useful as fuels and chemical feedstocks. Here we explore the potential of the 2-keto acid based biosynthesis in E. coli. We engineered E. coli to expand natural metabolism and produce target chemicals specifically and efficiently through systematic comparison of components in each step of the biosynthetic pathway. We paid close attention to carefully identify combinations of genes that would help enhance target chemical productivity, and also ensuring that there was limited chemical toxicity to the chosen host.

2-Keto acids based biosynthesis pathways for renewable fuels and chemicals

249th National Meeting (2015)

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