Document Detail

Pseudomonas aeruginosa directly shunts β-oxidation degradation intermediates into de novo fatty acid biosynthesis.
MedLine Citation:
PMID:  22753057     Owner:  NLM     Status:  MEDLINE    
We identified the fatty acid synthesis (FAS) initiation enzyme in Pseudomonas aeruginosa as FabY, a β-ketoacyl synthase KASI/II domain-containing enzyme that condenses acetyl coenzyme A (acetyl-CoA) with malonyl-acyl carrier protein (ACP) to make the FAS primer β-acetoacetyl-ACP in the accompanying article (Y. Yuan, M. Sachdeva, J. A. Leeds, and T. C. Meredith, J. Bacteriol. 194:5171-5184, 2012). Herein, we show that growth defects stemming from deletion of fabY can be suppressed by supplementation of the growth media with exogenous decanoate fatty acid, suggesting a compensatory mechanism. Fatty acids eight carbons or longer rescue growth by generating acyl coenzyme A (acyl-CoA) thioester β-oxidation degradation intermediates that are shunted into FAS downstream of FabY. Using a set of perdeuterated fatty acid feeding experiments, we show that the open reading frame PA3286 in P. aeruginosa PAO1 intercepts C(8)-CoA by condensation with malonyl-ACP to make the FAS intermediate β-keto decanoyl-ACP. This key intermediate can then be extended to supply all of the cellular fatty acid needs, including both unsaturated and saturated fatty acids, along with the 3-hydroxyl fatty acid acyl groups of lipopolysaccharide. Heterologous PA3286 expression in Escherichia coli likewise established the fatty acid shunt, and characterization of recombinant β-keto acyl synthase enzyme activity confirmed in vitro substrate specificity for medium-chain-length acyl CoA thioester acceptors. The potential for the PA3286 shunt in P. aeruginosa to curtail the efficacy of inhibitors targeting FabY, an enzyme required for FAS initiation in the absence of exogenous fatty acids, is discussed.
Yanqiu Yuan; Jennifer A Leeds; Timothy C Meredith
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Publication Detail:
Type:  Journal Article     Date:  2012-06-29
Journal Detail:
Title:  Journal of bacteriology     Volume:  194     ISSN:  1098-5530     ISO Abbreviation:  J. Bacteriol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-11     Completed Date:  2012-11-23     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  2985120R     Medline TA:  J Bacteriol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5185-96     Citation Subset:  IM    
Infectious Diseases Area, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
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MeSH Terms
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / classification,  metabolism
Cloning, Molecular
Escherichia coli / genetics,  metabolism
Fatty Acids / biosynthesis*,  chemistry
Gene Expression Regulation, Bacterial / physiology
Genetic Complementation Test
Molecular Structure
Pseudomonas aeruginosa / genetics,  metabolism*
Reg. No./Substance:
0/Fatty Acids; EC Synthase
Comment In:
J Bacteriol. 2012 Oct;194(19):5159-61   [PMID:  22821980 ]

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