S39: Structural and functional studies of emerging polyheterocyclic antibiotics

Chemical and biological approaches have uncovered a novel family of natural products. The hallmark of this family is thiazole and (methyl)oxazole heterocyles, which are derived from Cys and Ser/Thr residues of a ribosomally produced precursor peptide. To date, we have identified >500 orthologous biosynthetic gene clusters that produce such compounds, now termed the thiazole/oxazole-modified microcins (TOMMs). During TOMM biosynthesis, the unstructured, inactive precursor peptide is converted to a biologically active compound by the action of a trimeric, BCD synthetase complex. First, a cyclodehydratase catalyzes the formation of azolines from Cys/Ser/Thr with consumption of ATP. In a second reaction, a dehydrogenase oxidizes the heterocycle to afford the azole. This talk focuses on the elucidation of the molecular structure, biosynthetic pathway, and biological function of a plantazolicin, a recently described TOMM.