Natural Product Diversification Mediated by Alternative Transcriptional Starting

Angew Chem Int Ed Engl. 2018 May 14;57(20):5699-5702. doi: 10.1002/anie.201713199. Epub 2018 Apr 14.

Abstract

Photorhabdus luminescens dedicates a significant proportion of its genome to the production of natural products. These products and the structural variation in their derivatives may occur by a number of well-described mechanisms, such as module skipping or precursor promiscuity. Cappable-seq was used to identify transcriptional start sites of many of the gene clusters present in P. luminescens TTO1. We discovered that variations associated with the non-ribosomal peptide synthetase Kol, which is responsible for kolossin A production, possessed a number of internal transcripts that lead to synthesis of the smaller kolossin derivatives kolossin B and C. The data here support a new mechanism of natural product biosynthetic variation whereby mRNA may code for shorter NRPS enzymes in addition to full-length proteins, resulting in the production of smaller peptide derivatives.

Keywords: Cappable-seq; mass spectrometry; metabolomics; natural products; secondary metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Molecular Conformation
  • Peptide Synthases / chemistry
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism*
  • Photorhabdus / chemistry*
  • Photorhabdus / metabolism

Substances

  • Biological Products
  • Peptide Synthases
  • non-ribosomal peptide synthase