TY - JOUR
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.
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/6
Y1 - 2017/12/6
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.7b08492
DO - 10.1021/jacs.7b08492
M3 - Article
C2 - 29039940
AN - SCOPUS:85037539246
SN - 0002-7863
VL - 139
SP - 17438
EP - 17445
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 48
ER -