title: Induced biosynthesis of cryptic polyketide metabolites in a Burkholderia thailandensis quorum sensing mutant.
abstract: 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.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Keishi
authors.initials: K
authors.lastname: Ishida
authors.forename: Thorger
authors.initials: T
authors.lastname: Lincke
authors.forename: Swantje
authors.initials: S
authors.lastname: Behnken
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins