Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.

  title={Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.},
  author={Paul G. Arnison and Mervyn J. Bibb and Gabriele Bierbaum and Albert A. Bowers and Tim S. Bugni and Grzegorz Bulaj and Julio A. Camarero and Dominic J. Campopiano and Gregory L. Challis and Jon Clardy and Paul D. Cotter and David J. Craik and Michael J. Dawson and Elke Dittmann and Stefano Donadio and Pieter C. Dorrestein and Karl-D. Entian and Michael A. Fischbach and John S. Garavelli and Ulf G{\"o}ransson and Christian W. Gruber and Daniel H. Haft and Thomas K. Hemscheidt and C. Hertweck and Colin Hill and Alexander R. Horswill and Marcel Jaspars and Wendy L Kelly and Judith P. Klinman and Oscar P. Kuipers and A. James Link and Wen Liu and Mohamed A. Marahiel and Douglas A. Mitchell and Gert N. Moll and Bradley S. Moore and Rolf M{\"u}ller and Satish K. Nair and Ingolf F. Nes and Gillian E. Norris and Baldomero M. Olivera and Hiroyasu Onaka and Mark L. Patchett and Joern Piel and Martin J T Reaney and Sylvie Rebuffat and Reynolds Paul Ross and H. -G. Sahl and Eric W. Schmidt and Michael E. Selsted and Konstantin V. Severinov and Ben Shen and Kaarina Sivonen and Leif Smith and Torsten Stein and Roderich D. S{\"u}ssmuth and John R. Tagg and Gong-Li Tang and Andrew W. Truman and John C. Vederas and Christopher T Walsh and Jonathan D. Walton and Silke C Wenzel and Joanne M. Willey and Wilfred A. van der Donk},
  journal={Natural product reports},
  volume={30 1},
This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed. 

Ribosomally synthesized and post-translationally modified peptide natural products: new insights into the role of leader and core peptides during biosynthesis.

It is proposed that the leader peptides function as allosteric regulators that bind the active form of the biosynthetic enzymes in a conformational selection process, and how enzymes that generate polycyclic products of defined topologies may have been selected for during evolution.

Expanding the Structural Space of Ribosomal Peptides: Autocatalytic N-Methylation in Omphalotin Biosynthesis.

Tail-Me: The N-methylation of backbone amide bonds in peptide natural products was thought to be exclusive to non-ribosomal peptides, but a newly discovered methylation mechanism now brings this structural feature into the world of ribosomally synthesized and post-translationally modified peptides (RiPPs).

Decoding and recoding the ribosomal peptide universe.

  • E. Schmidt
  • Biology, Chemistry
    Chemistry & biology
  • 2012

Unveiling the Biosynthetic Pathway of the Ribosomally Synthesized and Post-translationally Modified Peptide Ustiloxin B in Filamentous Fungi.

The biosynthetic machinery of the first fungal ribosomally synthesized and post-translationally modified peptide (RiPP) ustiloxin B was elucidated through a series of gene inactivation and heterologous expression studies, providing new insight into the expression of the RiPP gene clusters found in various fungi.

Mechanisms of action of ribosomally synthesized and posttranslationally modified peptides (RiPPs)

This review highlights examples of the molecular mechanisms of action of RiPPs: ribosomally synthesized and posttranslationally modified peptides that underly those bioactivities.

Enzymatic macrocyclization of ribosomally synthesized and posttranslational modified peptides via C-S and C-C bond formation.

Recent progress in the macrocyclization of RiPPs by C-S and C-C bond formation is summarized with a focus on the current understanding of the enzymatic mechanisms.

Structure and mechanism of lanthipeptide biosynthetic enzymes.




Using marine natural products to discover a protease that catalyzes peptide macrocyclization of diverse substrates.

PatG, a protease discovered in this analysis, cleaves variables, short peptides out of a precursor protein, and cyclizes these peptides in vivo and in vitro.

Congeneric lantibiotics from ribosomal in vivo peptide synthesis with noncanonical amino acids.

Expanded repetoire: Synthetic amino acids translated into propeptides dramatically increase the chemical diversity of the two-component lantibiotic lichenicidin. This opens new routes towards novel

Ribosomal route to small-molecule diversity.

The cyanobactin ribosomal peptide (RP) natural product pathway was manipulated to incorporate multiple tandem mutations and non-proteinogenic amino acids, using eight heterologous components

Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds.

The major structural and biosynthetic categories of ribosomally synthesized bacterial natural products and, where applicable, compare them to their homologs from nonribosomal biosynthesis are summarized.

Follow the leader: the use of leader peptides to guide natural product biosynthesis.

This work reviews the available information for how the peptide sequences in the precursors govern the post-translational tailoring processes for several classes of natural products and highlights the great potential these leader peptide-directed biosynthetic systems offer for engineering conformationally restrained and pharmacophore-rich products with structural diversity that greatly expands the proteinogenic repertoire.

Genome mining for ribosomally synthesized natural products.

Circular logic: nonribosomal peptide-like macrocyclization with a ribosomal peptide catalyst.

A protease from ribosomal peptide biosynthesis macrocyclizes diverse substrates, including those resembling nonribosomal Peptide and hybrid polyketide-peptide products, using amide bonds rather than thioesters.

Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin

A biosynthetic gene cluster for thiocillin is reported and it is established that it, and by extension the whole class, is ribosomally synthesized.

Lasso peptides: structure, function, biosynthesis, and engineering.

This review describes the structure and function of all known lasso peptides (as of mid-2012) and covers the current knowledge about the biosynthesis of those molecules.

An Engineered Lantibiotic Synthetase That Does Not Require a Leader Peptide on Its Substrate

It is shown that fusing the leader peptide for the lantibiotic lacticin 481 to its biosynthetic enzyme LctM allows the protein to act on core peptides without a leader peptides.