ATP drives direct photosynthetic production of 1-butanol in cyanobacteria

Proceedings of the National Academy of Sciences of the United States of America - Tập 109 Số 16 - Trang 6018-6023 - 2012
Ethan I. Lan1,2, James C. Liao1,3,4
1Biomedical Engineering Interdepartmental Program, and
2Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA
3Department of Chemical and Biomolecular Engineering
4Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095

Tóm tắt

While conservation of ATP is often a desirable trait for microbial production of chemicals, we demonstrate that additional consumption of ATP may be beneficial to drive product formation in a nonnatural pathway. Although production of 1-butanol by the fermentative coenzyme A (CoA)-dependent pathway using the reversal of β-oxidation exists in nature and has been demonstrated in various organisms, the first step of the pathway, condensation of two molecules of acetyl-CoA to acetoacetyl-CoA, is thermodynamically unfavorable. Here, we show that artificially engineered ATP consumption through a pathway modification can drive this reaction forward and enables for the first time the direct photosynthetic production of 1-butanol from cyanobacteria Synechococcus elongatus PCC 7942. We further demonstrated that substitution of bifunctional aldehyde/alcohol dehydrogenase (AdhE2) with separate butyraldehyde dehydrogenase (Bldh) and NADPH-dependent alcohol dehydrogenase (YqhD) increased 1-butanol production by 4-fold. These results demonstrated the importance of ATP and cofactor driving forces as a design principle to alter metabolic flux.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 109 Số 16

6018-6023

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