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Metab Eng. 2008 Nov;10(6):312-20. doi: 10.1016/j.ymben.2008.08.001. Epub 2008 Aug 17.

Metabolic engineering of Escherichia coli for 1-butanol and 1-propanol production via the keto-acid pathways.

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Department of Chemical and Biomolecular Engineering, University of California, 5531 Boelter Hall, Los Angeles, CA 90095, USA.


Production of higher alcohols via the keto-acid intermediates found in microorganism's native amino-acid pathways has recently shown promising results. In this work, an Escherichia coli strain that produces 1-butanol and 1-propanol from glucose was constructed. The strain first converts glucose to 2-ketobutyrate, a common keto-acid intermediate for isoleucine biosynthesis. Then, 2-ketobutyrate is converted to 1-propanol through reactions catalyzed by the heterologous decarboxylase and dehydrogenase, or to 1-butanol via the chemistry involved in the synthesis of the unnatural amino acid norvaline. We systematically improved the synthesis of 1-propanol and 1-butanol through deregulation of amino-acid biosynthesis and elimination of competing pathways. The final strain demonstrated a production titer of 2 g/L with nearly 1:1 ratio of butanol and propanol.

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