Genomics-Driven Discovery of Myxopyromides, a Class of Polyketidic Amides Associated with Predation ofMyxococcussp. SDU36

Abstract

ABSTRACTMyxobacteria are renowned for their genuine prowess to deliver multifarious bioactive natural products. Genome mining ofMyxococcussp. SDU36 identified a hybrid PKS-NRPS BGC (mpd) that presumably specified previously uncharacterized molecules. The expression ofmpdwas activated by exchanging the innate promoter of core PKS-NRPS genes with our recently characterized strong constitutive promoter BBa_J23104. Comparative metabolic profiling allowed facile isolation of the elicited compounds1–5designated myxopyromides A–E, a group of structurally related polyketidic amides. Especially, myxopyromides D was appended with an uncommon pyrrolinone warhead at the carboxylic terminus, whereas myxopyromide C was instead decorated with a rare structural unit of aminobutanone. Although myxopyromides basically follow a textbook modular PKS-NRPS biosynthetic trajectory, an anteriorly unappreciated flexible chain release strategy is adopted to enrich the chemical repertoire ofmpdBGC. Interestingly, myxopyromides were associated with the predation ofMyxococcussp. SDU36.Abstract Figure