ATP drives direct photosynthetic production of 1-butanol in cyanobacteria

Ethan I. Lan, James C. Liao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

Abstract

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 coenzymeA (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.

Original languageEnglish
Pages (from-to)6018-6023
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number16
DOIs
StatePublished - 17 Apr 2012

Keywords

  • Biofuel
  • Malonyl-CoA
  • Metabolic engineering
  • Synthetic biology

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