Mutasynthesis-derived myxalamids and origin of the isobutyryl-CoA starter unit of myxalamid B.

Myxalamids are potent inhibitors of the eukaryotic electron transport chain produced by different myxobacteria. Here, we describe the identification of the myxalamid biosynthesis gene cluster from Myxococcus xanthus. Additionally, new myxalamids (5-13) have been obtained by mutasynthesis from bkd mutants of M. xanthus and Stigmatella aurantiaca. Moreover, as these bkd mutants are still able to produce myxalamid B (2), the origin of the isobutyryl-CoA (IB-CoA) starter unit required for its biosynthesis has been determined. In a M. xanthus bkd mutant, IB-CoA originates from valine, but in S. aurantiaca this starter unit is derived from alpha-oxidation of iso-odd fatty acids, thereby connecting primary and secondary metabolism.