Various gram-negative pathogenic bacteria use fatty acids of medium chain length collectively called Diffusible Signal Factors (DSFs) as quorum-sensing molecules to regulate virulence and biofilm formation in response to the local cell concentration.  The pathway of DSF biosynthesis was unclear since these fatty acids contain an unusual cis-2 double bond.  We report that cis-2-dodecenoic acid (called BDSF), the DSF of the human pathogen Burkholderia cenocepacia, is synthesized from the 3-hydroxydodecanoyl-acyl carrier protein intermediate of fatty acid synthesis by intercession of a protein, Bcam0581, that is a homologue of the classical b-oxidation enzyme crotonase. Bcam0581 has both dehydratase activity and thioesterase activity.  Both activities are abolished by mutagenesis of active site residues identified by alignment with rat mitochondrial crotonase.  Although dehydratase/hydratase activity is the classical crotonase reaction and two instances of thioesterases that are crotonase superfamily members have been reported, this is the first such enzyme that has both activities.  The chemical and biological advantages of BDSF synthesis such a bifunctional enzyme will be discussed.

BDSF quorum sensing molecule is synthesized by a bifunctional crotonase homologue that has both dehydratase and thioesterase activities

243rd National Meeting (2012)

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