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The Promiscuous Activity of the Radical SAM Enzyme NosL toward Two Unnatural Substrates
Author(s) -
Yin Yue,
Ji Xinjian,
Zhang Qi
Publication year - 2021
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.202100304
Subject(s) - chemistry , stereochemistry , moiety , tryptamine , cleave , bond cleavage , tryptophan , enzyme , tyrosine , peptide bond , cleavage (geology) , peptide , carboxylate , biochemistry , amino acid , catalysis , engineering , geotechnical engineering , fracture (geology)
Main observation and conclusion The radical S‐adenosylmethionine (SAM) enzyme NosL catalyzes the conversion of L ‐tryptophan ( L ‐Trp, 1) to 3‐methyl‐2‐indolic acid (MIA, 2), a key intermediate in the biosynthesis of the peptide antibiotic nosiheptide. Previous study showed that this remarkable recombination reaction starts from the cleavage of the Cα—COO – bond to result in a •CO 2 − radical migration. In contrast to the radical SAM tyrosine lyases, NosL appears unable to cleave the Cα—Cβ bond, which is intrinsically more favorable to be cleaved than the Cα—COO – bond. In this study, we investigate the NosL activity with tryptamine (11) and tryptophol (12), two L ‐Trp analogues lacking a carboxylate moiety. We showed that NosL cleaves the C1—C2 bond of these two substrates to produce 3‐methylindole (7), suggesting that the enzyme can still catalyze a β‐scission when the carboxyl group of Trp is absent. We also showed the enzyme exhibits a promiscuous activity, initiating the reaction by abstracting hydrogen atoms from two different sites to produce two sets of products.