Article

ATP drives direct photosynthetic production of 1-butanol in cyanobacteria.

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
Proceedings of the National Academy of Sciences (impact factor: 9.68). 04/2012; 109(16):6018-23. DOI:10.1073/pnas.1200074109 pp.6018-23
Source: PubMed

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 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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Keywords

1-butanol production
 
additional consumption
 
artificially engineered ATP consumption
 
bifunctional aldehyde/alcohol dehydrogenase
 
CoA)-dependent pathway
 
cyanobacteria Synechococcus elongatus PCC 7942
 
design principle
 
desirable trait
 
direct photosynthetic production
 
drive product formation
 
fermentative coenzyme
 
first step
 
metabolic flux
 
microbial production
 
NADPH-dependent alcohol dehydrogenase
 
nonnatural pathway
 
pathway
 
pathway modification
 
separate butyraldehyde dehydrogenase
 
substitution