Natural Product Diversification Mediated by Alternative Transcriptional Starting.

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.