Discovery and metabolic origin of 4,4ʹ-dihydroxy-3,3ʹ,5,5ʹ-tetrachlorobenzophenone from a <i>Burkholderia oklahomensis</i> clinical isolate

Abstract Burkholderia oklahomensis LMG 23618 T is a B. pseudomallei -like bacterium originally isolated in 1973 from a wound infection caused by a farming accident in Oklahoma. Metabolic profiling of an organic extract from cultures of B . oklahomensis LMG 23618 T using UHPLC-ESI-Q-ToF-MS led to identification of three known metabolites, betulinan A, yersiniabactin and ulbactin B, in addition to a novel polychlorinated compound. Mass-directed purification enabled isolation of the novel specialized metabolite, which was shown by X-ray crystallography and NMR spectroscopic analysis to be 4,4ʹ-dihydroxy-3,3ʹ,5,5ʹ-tetrachlorobenzophenone. Feeding experiments with stable isotope-labelled precursors established that the carbon skeleton of this unusual metabolite derives from two molecules of tyrosine. This led us to propose a plausible biosynthetic pathway via decarboxylative condensation of 3, 5-dichloro-4-hydroxybenzoic acid with its coenzyme A thioester derivative. The absolute configuration of ulbactin B was also established as 4ʹR, 3ʺS, 7ʺS, 8ʺR using X-ray crystallography and NMR spectroscopy.