Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products
Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α- N -methyl groups are installed by a methyltransferase fused to the precursor peptide substrate. Peptide backbone N-methylation, as seen in cyclosporin A, has been...
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| Veröffentlicht in: | Nature chemical biology 2017-08, Vol.13 (8), p.833-835 |
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| creator | van der Velden, Niels S Kälin, Noemi Helf, Maximilian J Piel, Jörn Freeman, Michael F Künzler, Markus |
| description | Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α-
N
-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.
Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus
Omphalotus olearius
. We show that iterative autocatalytic activity of an
N
-methyltransferase fused to its peptide substrate is the signature of a new family of ribosomally encoded metabolites. |
| doi_str_mv | 10.1038/nchembio.2393 |
| format | Article |
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N
-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.
Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus
Omphalotus olearius
. We show that iterative autocatalytic activity of an
N
-methyltransferase fused to its peptide substrate is the signature of a new family of ribosomally encoded metabolites.</description><identifier>ISSN: 1552-4450</identifier><identifier>EISSN: 1552-4469</identifier><identifier>DOI: 10.1038/nchembio.2393</identifier><identifier>PMID: 28581484</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>38/23 ; 38/44 ; 45/77 ; 45/88 ; 45/90 ; 631/92/349 ; 631/92/458 ; 631/92/60 ; 631/92/611 ; 82/58 ; 82/80 ; 82/83 ; Agaricales - chemistry ; Backbone ; Biocatalysis ; Biochemical Engineering ; Biochemistry ; Biological Products - chemistry ; Biological Products - metabolism ; Bioorganic Chemistry ; brief-communication ; Catalysis ; Cell Biology ; Chemistry ; Chemistry/Food Science ; Cyclosporin A ; DNA methylation ; Fungi ; Metabolites ; Methylation ; Methyltransferase ; Methyltransferases - chemistry ; Methyltransferases - metabolism ; Molecular Conformation ; N-Methyltransferase ; Natural products ; Peptides ; Peptides - chemistry ; Peptides - metabolism ; Post-translation ; Ribonucleic acid ; Ribosomes - chemistry ; Ribosomes - metabolism ; RNA</subject><ispartof>Nature chemical biology, 2017-08, Vol.13 (8), p.833-835</ispartof><rights>Springer Nature America, Inc. 2017</rights><rights>Copyright Nature Publishing Group Aug 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-9306ab412ec969a7b6629fa9cbd80e4d703034435706c3aa839fe746a79d39693</citedby><cites>FETCH-LOGICAL-c465t-9306ab412ec969a7b6629fa9cbd80e4d703034435706c3aa839fe746a79d39693</cites><orcidid>0000-0002-0491-9618 ; 0000-0003-1275-0629</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nchembio.2393$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nchembio.2393$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28581484$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Velden, Niels S</creatorcontrib><creatorcontrib>Kälin, Noemi</creatorcontrib><creatorcontrib>Helf, Maximilian J</creatorcontrib><creatorcontrib>Piel, Jörn</creatorcontrib><creatorcontrib>Freeman, Michael F</creatorcontrib><creatorcontrib>Künzler, Markus</creatorcontrib><title>Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products</title><title>Nature chemical biology</title><addtitle>Nat Chem Biol</addtitle><addtitle>Nat Chem Biol</addtitle><description>Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α-
N
-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.
Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus
Omphalotus olearius
. We show that iterative autocatalytic activity of an
N
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Academic</collection><jtitle>Nature chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Velden, Niels S</au><au>Kälin, Noemi</au><au>Helf, Maximilian J</au><au>Piel, Jörn</au><au>Freeman, Michael F</au><au>Künzler, Markus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products</atitle><jtitle>Nature chemical biology</jtitle><stitle>Nat Chem Biol</stitle><addtitle>Nat Chem Biol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>13</volume><issue>8</issue><spage>833</spage><epage>835</epage><pages>833-835</pages><issn>1552-4450</issn><eissn>1552-4469</eissn><abstract>Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α-
N
-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.
Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus
Omphalotus olearius
. We show that iterative autocatalytic activity of an
N
-methyltransferase fused to its peptide substrate is the signature of a new family of ribosomally encoded metabolites.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28581484</pmid><doi>10.1038/nchembio.2393</doi><tpages>3</tpages><orcidid>https://orcid.org/0000-0002-0491-9618</orcidid><orcidid>https://orcid.org/0000-0003-1275-0629</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 38/23 38/44 45/77 45/88 45/90 631/92/349 631/92/458 631/92/60 631/92/611 82/58 82/80 82/83 Agaricales - chemistry Backbone Biocatalysis Biochemical Engineering Biochemistry Biological Products - chemistry Biological Products - metabolism Bioorganic Chemistry brief-communication Catalysis Cell Biology Chemistry Chemistry/Food Science Cyclosporin A DNA methylation Fungi Metabolites Methylation Methyltransferase Methyltransferases - chemistry Methyltransferases - metabolism Molecular Conformation N-Methyltransferase Natural products Peptides Peptides - chemistry Peptides - metabolism Post-translation Ribonucleic acid Ribosomes - chemistry Ribosomes - metabolism RNA |
| title | Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products |
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