If mass spectra could talk: Molecular movies of covalent catalysis during bioassembly of diverse natural products

BIOL 110

Neil L. Kelleher, kelleher@scs.uiuc.edu, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
For several years, our laboratory has operated at the interface between mass spectrometry an enzymology. This career track was first initiated as a joint student between Tadhg Begley and Fred McLafferty. Most recently in Illinois, we have been applying and developing new methods for streamlined interrogation of covalent intermediates on “thiotemplate” enzymes responsible for non-ribosomal peptide synthesis (NRPS) and polyketide biosynthesis (PKS). In addition to near complete characterization of every intermediate in the yersiniabactin system, we have joined with the Walsh Laboratory to illuminate key questions in the biogenesis of (chlorinated) pyrroles in aminocoumarins and pyoluteorin, and the pksX gene cluster from B. subtilis. Intermediates at the intersection between primary and secondary metabolism have also been interrogated for both NRPS and PKS systems using new MS-based methods for quick determination of preferred substrates (i.e., multiplexed SAR by MS) that rely on fortuitous ion chemistry (i.e., ejection of a phosphopantethienyl arm).