Burkholderia thailandensis methylated hydroxy-alkylquinolines: biosynthesis and antimicrobial activity in co-culture experiments

The bacterium produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology of this soil-dwelling bacterium. In liquid co-culture experiments, secretes a previously unstudied antimicrobial that nearly eliminates another soil bacterium, . To identify the antimicrobial, we used a transposon mutagenesis approach. This screen identified antimicrobial-defective mutants with insertions in the and genes involved in biosynthesis of a family of quinolones called 3-methyl-4-hydroxy-2-alkenylquinolines (HMAQs), which are related to the 4-hydroxy-2-alkylquinolines (HAQs). Insertions also occurred in a previously uncharacterized gene BTH_II1576. We confirm that BTH_II1576 is involved in generating oxide HMAQ (HMAQ-NO) in and that HMAQ-NOs are sufficient to eliminate in co-cultures. Moreover, synthetic HMAQ-NO is ~50-fold more active than HMAQ. Both the methyl group and the length of the carbon side chain account for high activity of HMAQ-NO against The results provide new information on the biosynthesis and activities of HMAQs and reveal new insight into how these molecules might be important for the ecology of .