Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Radical-mediated enzymatic carbon chain fragmentation-recombination

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Zhang, Qinghai
  • Li, Yuxing
  • Chen, D. D.
  • Yu, Y.
  • Duan, L. A.
  • Shen, Ben
  • Liu, W.

publication date

  • March 2011

journal

  • Nature Chemical Biology  Journal

abstract

  • The radical S-adenosylmethionine (S-AdoMet) superfamily contains thousands of proteins that catalyze highly diverse conversions, most of which are poorly understood, owing to a lack of information regarding chemical products and radical-dependent transformations. We here report that NosL, involved in forming the indole side ring of the thiopeptide nosiheptide (NOS), is a radical S-AdoMet 3-methyl-2-indolic acid (MIA) synthase. NosL catalyzed an unprecedented carbon chain reconstitution of L-tryptophan to give MIA, showing removal of the Cα-N unit and shift of the carboxylate to the indole ring. Dissection of the enzymatic process upon the identification of products and a putative glycyl intermediate uncovered a radical-mediated, unusual fragmentation-recombination reaction. This finding unveiled a key step in radical S-AdoMet enzyme-catalyzed structural rearrangements during complex biotransformations. Additionally, NosL tolerated fluorinated L-tryptophan as the substrate, allowing for production of a regiospecifically halogenated thiopeptide that has not been found among the more than 80 members of the naturally occurring thiopeptide family.

subject areas

  • Binding Sites
  • Carbon
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Free Radicals
  • Indoles
  • Peptides
  • S-Adenosylmethionine
  • Substrate Specificity
  • Thiazoles
  • Time Factors
  • Tryptophan
scroll to property group menus

Identity

PubMed Central ID

  • PMC3079562

International Standard Serial Number (ISSN)

  • 1552-4450

Digital Object Identifier (DOI)

  • 10.1038/nchembio.512

PubMed ID

  • 21240261
scroll to property group menus

Additional Document Info

start page

  • 154

end page

  • 160

volume

  • 7

issue

  • 3

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support