Non-ribosomal peptide

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A non-ribosomal peptide ( NRP , English non-ribosomal peptide ) is a peptide that was not synthesized on ribosomes , but as a secondary metabolite by certain enzymes , the non-ribosomal peptide synthetases ( NRPS ).

In contrast to a non- ribosomal peptide, most peptides and proteins in a cell are produced ribosomally by protein biosynthesis , from proteinogenic amino acids according to genetic information . The enzymatically active proteins, the complexes of which are known as nonribosomal peptide synthetases, are also produced in this way. Such NRPS are found in various types of archaea , bacteria , fungi and, for example, also in nudibranchs . These peptide synthetases enable organisms to build peptides outside of genetically coded sequences , including non-proteinogenic amino acids, with high structural diversity and for diverse biological activities - as non- ribosomal peptide synthesis .

properties

Nonribosomal peptides are oligopeptides or smaller polypeptides that are generated by nonribosomal peptide synthetases independently of an RNA template. The previously known consist of up to 50 amino acids. The biosynthesis usually takes place step by step by means of modular multi-enzyme complexes and is specific for the respective peptide insofar as a synthetase can only catalyze certain synthesis steps. In non-ribosomal peptide synthesis, atypical amino acids are often used as building blocks, e.g. B. D-amino acids , β-amino acids or modified amino acids, some fatty acids are also used. The primary structure can be linear, but branches, bridges and cyclizations are not uncommon, and heterocyclic and polycyclic peptides also occur. NRPs have different functions, e.g. B. as antibiotic , pigments ( indigoidin ), siderophores ( enterobactin , myxochelin A , pyoverdine ) or toxins ( microcystin , nodularin , cyanotoxin , HC-toxin, AM-toxin, victorin). Some NRPs are virulence factors .

NRPs are listed in the freely accessible NORINE database .

Applications

Some antibiotics and their precursors ( actinomycin , bacitracin , daptomycin , vancomycin , tyrothricin and tyrocidin , gramicidin , zwittermicin A , ACV tripeptide , teixobactin ), cytostatics ( epothilones , bleomycin ) and immunosuppressants ( cyclosporin A ) are nonribosomal peptides. Through a protein design , non-ribosomal peptide synthetases can be specifically modified.

literature

Individual evidence

  1. ^ Li-Xin Dai: Kuiling Ding (ed.): Organic chemistry: breakthroughs and perspectives . Wiley-VCH, Weinheim, Germany 2012, ISBN 9783527333776 .
  2. ↑ Hao Wang, David Fewer, Liisa Holm, Leo Rouhiainen, Kaarina Sivonena: Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes . In: Proc Natl Acad Sci USA . Volume 111, No. 25, June 2014, pp. 9259-9264. PMC 4078802 (free full text).
  3. ↑ see entry Polytheonamide B in the NORINE database .
  4. ↑ a b Segolene Caboche, Maude Pupin, Valerie Leclere, Arnaud Fontaine, Philippe Jacques and Gregory Kucherov: Norine: a database of nonribosomal peptides . In: Nucleic Acids Research . 36 (Database issue), No. Database issue, 2008, pp. D326-31. doi : 10.1093 / nar / gkm792 . PMID 17913739 . PMC 2238963 (free full text).
  5. ↑ MA Marahiel: Working outside the protein synthesis rules: insights into non-ribosomal peptide synthesis. In: Journal of peptide science: an official publication of the European Peptide Society. Volume 15, Number 12, December 2009, pp. 799-807, ISSN  1099-1387 . doi : 10.1002 / psc.1183 . PMID 19827002 .
  6. ↑ MJ Calcott, JG Owen, IL Lamont, DF Ackerley: Biosynthesis of novel pyoverdines by domain substitution in a non-ribosomal peptide synthetase of Pseudomonas aeruginosa. In: Applied and environmental microbiology. [electronic publication before printing] July 2014, ISSN  1098-5336 . doi : 10.1128 / AEM.01453-14 . PMID 25015884 .
  7. ^ JD Walton: HC toxin . In: Phytochemistry . 67, No. 14, 2006, pp. 1406-1413. doi : 10.1016 / j.phytochem . 2006.05.033 . PMID 16839576 .
  8. ↑ RD Johnson, L. Johnson, Y. Itoh, M. Kodama, H. Otani, and K. Kohmoto: Cloning and Characterization of a Cyclic Peptide Synthetase Gene from Alternaria alternata Apple Pathotype Whose Product Is Involved in AM-Toxin Synthesis and Pathogenicity . In: Molecular Plant-Microbe Interactions . 13, No. 7, 2000, pp. 742-753. doi : 10.1094 / MPMI.2000.13.7.742 . PMID 10875335 .
  9. ^ JD Walton: Host-selective toxins: agents of compatibility. In: The Plant cell. Volume 8, Number 10, October 1996, pp. 1723-1733, ISSN  1040-4651 . doi : 10.1105 / tpc.8.10.1723 . PMID 8914323 . PMC 161310 (free full text).
  10. ↑ MJ Calcott, JG Owen, IL Lamont, DF Ackerley: Biosynthesis of novel pyoverdines by domain substitution in a non-ribosomal peptide synthetase of Pseudomonas aeruginosa. In: Applied and environmental microbiology. [electronic publication before printing] July 2014, ISSN  1098-5336 . doi : 10.1128 / AEM.01453-14 . PMID 25015884 .
  11. ↑ GH Hur, CR Vickery, MD Burkart: Explorations of catalytic domains in non-ribosomal peptide synthetase enzymology. In: Natural Product Reports . Volume 29, Number 10, October 2012, pp. 1074-1098, ISSN  1460-4752 . doi : 10.1039 / c2np20025b . PMID 22802156 .