NosN, a Radical S-Adenosylmethionine Methylase, Catalyzes Both C1 Transfer and Formation of the Ester Linkage of the Side-Ring System during the Biosynthesis of Nosiheptide

Joseph W. LaMattina, Bo Wang, Edward D. Badding, Lauren K. Gadsby, Tyler L. Grove, Squire J. Booker

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Nosiheptide, a member of the e series of macrocyclic thiopeptide natural products, contains a side-ring system composed of a 3,4-dimethylindolic acid (DMIA) moiety connected to Glu6 and Cys8 of the thiopeptide backbone via ester and thioester linkages, respectively. Herein, we show that NosN, a predicted class C radical S-adenosylmethionine (SAM) methylase, catalyzes both the transfer of a C1 unit from SAM to 3-methylindolic acid linked to Cys8 of a synthetic substrate surrogate as well as the formation of the ester linkage between Glu6 and the nascent C4 methylene moiety of DMIA. In contrast to previous studies that indicated that 5′-methylthioadenosine is the immediate methyl donor in the reaction, in our studies, SAM itself plays this role, giving rise to S-adenosylhomocysteine as a coproduct of the reaction.

Original languageEnglish (US)
Pages (from-to)17438-17445
Number of pages8
JournalJournal of the American Chemical Society
Volume139
Issue number48
DOIs
StatePublished - Dec 6 2017

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S-Adenosylmethionine
Biosynthesis
Esters
Acids
S-Adenosylhomocysteine
Biological Products
Substrates
nosiheptide

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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title = "NosN, a Radical S-Adenosylmethionine Methylase, Catalyzes Both C1 Transfer and Formation of the Ester Linkage of the Side-Ring System during the Biosynthesis of Nosiheptide",
abstract = "Nosiheptide, a member of the e series of macrocyclic thiopeptide natural products, contains a side-ring system composed of a 3,4-dimethylindolic acid (DMIA) moiety connected to Glu6 and Cys8 of the thiopeptide backbone via ester and thioester linkages, respectively. Herein, we show that NosN, a predicted class C radical S-adenosylmethionine (SAM) methylase, catalyzes both the transfer of a C1 unit from SAM to 3-methylindolic acid linked to Cys8 of a synthetic substrate surrogate as well as the formation of the ester linkage between Glu6 and the nascent C4 methylene moiety of DMIA. In contrast to previous studies that indicated that 5′-methylthioadenosine is the immediate methyl donor in the reaction, in our studies, SAM itself plays this role, giving rise to S-adenosylhomocysteine as a coproduct of the reaction.",
author = "LaMattina, {Joseph W.} and Bo Wang and Badding, {Edward D.} and Gadsby, {Lauren K.} and Grove, {Tyler L.} and Booker, {Squire J.}",
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NosN, a Radical S-Adenosylmethionine Methylase, Catalyzes Both C1 Transfer and Formation of the Ester Linkage of the Side-Ring System during the Biosynthesis of Nosiheptide. / LaMattina, Joseph W.; Wang, Bo; Badding, Edward D.; Gadsby, Lauren K.; Grove, Tyler L.; Booker, Squire J.

In: Journal of the American Chemical Society, Vol. 139, No. 48, 06.12.2017, p. 17438-17445.

Research output: Contribution to journalArticle

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T1 - NosN, a Radical S-Adenosylmethionine Methylase, Catalyzes Both C1 Transfer and Formation of the Ester Linkage of the Side-Ring System during the Biosynthesis of Nosiheptide

AU - LaMattina, Joseph W.

AU - Wang, Bo

AU - Badding, Edward D.

AU - Gadsby, Lauren K.

AU - Grove, Tyler L.

AU - Booker, Squire J.

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