Induced biosynthesis of cryptic polyketide metabolites in a Burkholderia thailandensis quorum sensing mutant.
Genetic manipulation of the LuxR-type quorum sensing regulator system in Burkholderia thailandensis caused a significant change in the metabolic profile: it led to activation of the thailandamide biosynthesis gene cluster, dramatically increased thailandamide production, and induced strong pigmentation. A novel polyketide metabolite, thailandamide lactone (2), which cannot be detected in the wild type, was isolated from the mutant broth, and its structure was elucidated by high-resolution mass spectrometry and IR and NMR spectroscopy. In a biological assay using tumor cell lines, 2 showed moderate antiproliferative activities. This finding not only points to complex regulation but also serves as a proof of concept that engineering quorum sensing mutants may enable the discovery of novel bioactive natural products encoded by silent or only weakly expressed biosynthetic pathway genes.
Ishida
Keishi
K
Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
Lincke
Thorger
T
Behnken
Swantje
S
Hertweck
Christian
C
D001426:Bacterial Proteins / Q000378:metabolism*; D019117:Burkholderia / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D053038:Quorum Sensing; D013055:Spectrophotometry, Infrared
D001426:Bacterial Proteins