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

Myxobacteria are renowned for their genuine prowess to deliver multifarious bioactive natural products. Genome mining of Myxococcus sp. SDU36 identified a hybrid PKS-NRPS BGC (mpd) that presumably specified previously uncharacterized molecules. The expression of mpd was 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 compounds 1-5 designated 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 of mpd BGC. Interestingly, myxopyromides were associated with the predation of Myxococcus sp. SDU36. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/535179v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@29d791org.highwire.dtl.DTLVardef@1079fdcorg.highwire.dtl.DTLVardef@19044d8org.highwire.dtl.DTLVardef@97c7dc_HPS_FORMAT_FIGEXP M_FIG C_FIG