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Substrate‐Tuned Catalysis of the Radical S ‐Adenosyl‐ L ‐Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis
Author(s) -
Ji Xinjian,
Li Yongzhen,
Ding Wei,
Zhang Qi
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201503976
Subject(s) - chemistry , stereochemistry , biosynthesis , enzyme , substrate (aquarium) , catalysis , enzyme catalysis , hydrogen atom abstraction , amino acid , methionine , benzofuran , biochemistry , radical , oceanography , geology
NosL is a radical S‐adenosyl‐ L ‐methionine (SAM) enzyme that converts L ‐Trp to 3‐methyl‐2‐indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2‐amino‐3‐(benzofuran‐3‐yl)propanoic acid (ABPA), we clearly demonstrated that the 5′‐deoxyadenosyl (dAdo) radical‐mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L ‐Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical‐mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.