Biosynthetic Pathway of Pseudomonas aeruginosa 4-Hydroxy-2-Alkylquinolines

Abstract

ABSTRACT The role of intercellular communication in the regulation of bacterial multicellular behavior has received widespread attention, and a variety of signal molecules involved in bacterial communication have been discovered. In addition to the N -acyl-homoserine lactones, 4-hydroxy-2-alkylquinolines (HAQs), including the Pseudomonas quinolone signal, have been shown to function as signal molecules in Pseudomonas aeruginosa . In this study we unraveled the biosynthetic pathway of HAQs using feeding experiments with isotope-labeled precursors and analysis of extracted HAQs by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Our results show that the biosynthesis of various HAQ metabolites is directed via a common metabolic pathway involving a “head-to-head” condensation of anthranilic acid and β-keto fatty acids. Moreover, we provide evidence that the β-keto-(do)decanoic acids, crucial for the biosynthesis of the heptyl and nonyl derivatives of the 4-hydroxyquinolines in P. aeruginosa , are at least in part derived from a common pool of β-hydroxy(do)decanoic acids involved in rhamnolipid biosynthesis.