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

Microbiology. 2002 Dec;148(Pt 12):3849-3856. doi: 10.1099/00221287-148-12-3849.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / metabolism*
  • Acylation
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / isolation & purification
  • Alcohol Oxidoreductases / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Fatty Acids / biosynthesis*
  • Gene Expression Regulation, Bacterial*
  • Ligases / genetics
  • Ligases / metabolism
  • Mutation
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / growth & development
  • Signal Transduction


  • Bacterial Proteins
  • Fatty Acids
  • LasI protein, Pseudomonas aeruginosa
  • homoserine lactone
  • Alcohol Oxidoreductases
  • acetoacetyl-CoA reductase
  • Ligases
  • N-acylhomoserine lactone synthase
  • 4-Butyrolactone