DOI: 10.5061/dryad.7q830
title: Data from: The genomic landscape of ribosomal peptides containing thiazole and oxazole heterocycles

description: Background: Ribosomally synthesized and post-translationally modified
 peptides (RiPPs) are a burgeoning class of natural products with diverse
 activity that share a similar origin and common features in their
 biosynthetic pathways. The precursor peptides of these natural products
 are ribosomally produced, upon which a combination of modification enzymes
 installs diverse functional groups. This genetically encoded peptide-based
 strategy allows for rapid diversification of these natural products by
 mutation in the precursor genes merged with unique combinations of
 modification enzymes. Thiazole/oxazole-modified microcins (TOMMs) are a
 class of RiPPs defined by the presence of heterocycles derived from
 cysteine, serine, and threonine residues in the precursor peptide. TOMMs
 encompass a number of different families, including but not limited to the
 linear azol(in)e-containing peptides (streptolysin S, microcin B17, and
 plantazolicin), cyanobactins, thiopeptides, and bottromycins. Although
 many TOMMs have been explored, the increased availability of genome
 sequences has illuminated several unexplored TOMM producers. Methods: All
 YcaO domain-containing proteins (D protein) and the surrounding genomic
 regions were were obtained from the European Molecular Biology Laboratory
 (EMBL) and the European Bioinformatics Institute (EBI). MultiGeneBlast was
 used to group gene clusters contain a D protein. A number of techniques
 were used to identify TOMM biosynthetic gene clusters from the D protein
 containing gene clusters. Precursor peptides from these gene clusters were
 also identified. Both sequence similarity and phylogenetic analysis were
 used to classify the 20 diverse TOMM clusters identified. Results: Given
 the remarkable structural and functional diversity displayed by known
 TOMMs, a comprehensive bioinformatic study to catalog and classify the
 entire RiPP class was undertaken. Here we report the bioinformatic
 characterization of nearly 1,500 TOMM gene clusters from genomes in the
 European Molecular Biology Laboratory (EMBL) and the European
 Bioinformatics Institute (EBI) sequence repository. Genome mining suggests
 a complex diversification of modification enzymes and precursor peptides
 to create more than 20 distinct families of TOMMs, nine of which have not
 heretofore been described. Many of the identified TOMM families have an
 abundance of diverse precursor peptide sequences as well as unfamiliar
 combinations of modification enzymes, signifying a potential wealth of
 novel natural products on known and unknown biosynthetic scaffolds.
 Phylogenetic analysis suggests a widespread distribution of TOMMs across
 multiple phyla; however, producers of similar TOMMs are generally found in
 the same phylum with few exceptions. Conclusions: The comprehensive genome
 mining study described herein has uncovered a myriad of unique TOMM
 biosynthetic clusters and provides an atlas to guide future discovery
 efforts. These biosynthetic gene clusters are predicted to produce diverse
 final products, and the identification of additional combinations of
 modification enzymes could expand the potential of combinatorial natural
 product biosynthesis.
description: YcaO containing organism
 16S alignmentThe alignment used to
 create the trees in Figure 6 and S8. These trees contain the 16S sequences
 from all of the organisms containing a YcaO domain protein used in the
 study.141119-16sMafftOut.meg16S maximum likelihood tree from TOMM producersA maximum likelihood tree made with the 16S sequences from all organisms that contain a YcaO domain containing protein. This tree was used in Figure 6 and S8, but colored differently in the paper depending on TOMM produced141218-16s-knowns-maximum.nwkYcaO containing protein alignmentAn alignment of all YcaO containing (D) proteins that were used in the analysis. This alignment was used to generate Figures S3 and S4141219-DOnlyTreeMuscle.megMaximum likelihood tree with YcaO containing protiensThis is a Maximum likelihood tree with all the YcaO domain containing (D) proteins used in this study. This tree was used to create Figures S3 and S4, but colored differently depending on the TOMM created.141230-AllDMaximum-knowns.nwk