Biosynthesis of Cittilins, Unusual Ribosomally Synthesized and Post-translationally Modified Peptides from Myxococcus xanthus
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Hug, Joachim J.Dastbaz, Jan
Adam, Sebastian
Revermann, Ole
Koehnke, Jesko
Krug, Daniel
Müller, Rolf
Issue Date
2020-07-08
Metadata
Show full item recordAbstract
Cittilins are secondary metabolites from myxobacteria comprised of three l-tyrosines and one l-isoleucine forming a bicyclic tetrapeptide scaffold with biaryl and aryl-oxygen-aryl ether bonds. Here we reveal that cittilins belong to the ribosomally synthesized and post-translationally modified peptide (RiPP) family of natural products, for which only the crocagins have been reported from myxobacteria. A 27 amino acid precursor peptide harbors a C-terminal four amino acid core peptide, which is enzymatically modified and finally exported to yield cittilins. The small biosynthetic gene cluster responsible for cittilin biosynthesis also encodes a cytochrome P450 enzyme and a methyltransferase, whereas a gene encoding a prolyl endopeptidase for the cleavage of the precursor peptide is located outside of the cittilin biosynthetic gene cluster. We confirm the roles of the biosynthetic genes responsible for the formation of cittilins using targeted gene inactivation and heterologous expression in Streptomyces ssp. We also report first steps toward the biochemical characterization of the proposed biosynthetic pathway in vitro. An investigation of the cellular uptake properties of cittilin A connected it to a potential biological function as an inhibitor of the prokaryotic carbon storage regulator A (CsrA).Citation
ACS Chem Biol. 2020;15(8):2221-2231. doi:10.1021/acschembio.0c00430.Affiliation
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.Publisher
American Chemical Society (ACS)Journal
ACS chemical biologyPubMed ID
32639716Type
ArticleLanguage
enISSN
1554-8929EISSN
1554-8937Sponsors
Bundesministerium für Bildung und Forschungae974a485f413a2113503eed53cd6c53
10.1021/acschembio.0c00430
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
Related articles
- Structure and Biosynthesis of Crocagins: Polycyclic Posttranslationally Modified Ribosomal Peptides from Chondromyces crocatus.
- Authors: Viehrig K, Surup F, Volz C, Herrmann J, Abou Fayad A, Adam S, Köhnke J, Trauner D, Müller R
- Issue date: 2017 Jun 19
- Characterization of the Stereoselective P450 Enzyme BotCYP Enables the <i>In Vitro</i> Biosynthesis of the Bottromycin Core Scaffold.
- Authors: Adam S, Franz L, Milhim M, Bernhardt R, Kalinina OV, Koehnke J
- Issue date: 2020 Dec 9
- Discovery and characterization of a novel C-terminal peptide carboxyl methyltransferase in a lassomycin-like lasso peptide biosynthetic pathway.
- Authors: Su Y, Han M, Meng X, Feng Y, Luo S, Yu C, Zheng G, Zhu S
- Issue date: 2019 Mar
- Salinipeptins: Integrated Genomic and Chemical Approaches Reveal Unusual d-Amino Acid-Containing Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) from a Great Salt Lake Streptomyces sp.
- Authors: Shang Z, Winter JM, Kauffman CA, Yang I, Fenical W
- Issue date: 2019 Mar 15
- The Creatininase Homolog MftE from <i>Mycobacterium smegmatis</i> Catalyzes a Peptide Cleavage Reaction in the Biosynthesis of a Novel Ribosomally Synthesized Post-translationally Modified Peptide (RiPP).
- Authors: Bruender NA, Bandarian V
- Issue date: 2017 Mar 10