Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a growing class of natural products and have attracted attention because of their easily programmable scaffolds through alteration of precursor peptide sequences. This programmability is dependent on maintaining conserved recognition motifs in the N-terminal half of the precursor peptide called the leader peptide. Here, we probed leader peptide recognition in the biosynthesis of the highly discriminating antibiotic Plantazolicin (PZN). The PZN precursor peptide (BamA) has azole heterocycles installed by a trimeric synthetase complex (BamBCD) through cyclization and subsequent oxidation of Cys, Ser, Thr residues. We identified P7 and L11 of the leader peptide as crucial recognition elements with alanine scanning mutagenesis and fluorescence polarization binding assays. In vitro synthetase reactions and in vivo production levels further support a PxxL binding motif in the leader. Additionally, we found that leader peptide recognition within the PZN family is mediated by PznC with PznB/D likely playing allosteric roles.

Precursor peptide recognition in the biosynthesis of plantazolicin antibiotics

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.