Beta-ketoacyl acyl carrier protein reductase (FabG) activity of the fatty acid biosynthetic pathway is a determining factor of 3-oxo-homoserine lactone acyl chain lengths.
The two acyl-homoserine lactones (AHLs) N-(butyryl)-L-homoserine lactone and N-[3-oxododecanoyl]-L-homoserine lactone (3-oxo-C(12)-HSL) are required for quorum sensing in Pseudomonas aeruginosa. These AHLs derive their invariant lactone rings from S-adenosylmethionine and their variable acyl chains from the cellular acyl-acyl carrier protein (ACP) pool. This reaction is catalysed by specific AHL synthases, which exhibit acyl chain specificity. Culture supernatants of P. aeruginosa contain multiple 3-oxo-AHLs that differ in their acyl chain lengths but their physiological role, if any, remains unknown. An in vitro fatty acid-3-oxo-AHL synthesis system was established utilizing purified P. aeruginosa Fab proteins, ACP and the LasI 3-oxo-AHL synthase. In the presence of excess protein, substrates and cofactors, this system produced almost exclusively 3-oxo-C(12)-HSL. When the beta-ketoacyl-ACP reductase (FabG) catalysed step was made rate-limiting by switching from the preferred NADPH cofactor to NADH, increased levels of short chain 3-oxo-AHLs were produced, presumably because shorter-chain ketoacyl-ACPs accumulated and thus became LasI substrates. Consistent with these in vitro observations, a fabG(Ts) mutant produced increased amounts of 3-oxo-AHLs in vivo. Thus, in vitro and in vivo evidence indicated that modulation of FabG activity of the fatty acid biosynthetic pathway may determine the acyl chain lengths of these 3-oxo-AHLs and that the LasI 3-oxo-AHL synthase is sufficient for their synthesis.
Hoang
Tung T
TT
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682A, USA1.
Sullivan
Sarah A
SA
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682A, USA1.
Cusick
John K
JK
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682A, USA1.
Schweizer
Herbert P
HP
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682A, USA1.
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D000215:Acylation; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D015398:Signal Transduction
D001426:Bacterial Proteins; D005227:Fatty Acids; C081237:LasI protein, Pseudomonas aeruginosa; C088386:homoserine lactone; D000429:Alcohol Oxidoreductases; C023744:acetoacetyl-CoA reductase; D008025:Ligases; C449816:N-acylhomoserine lactone synthase; D015107:4-Butyrolactone