Regioselective Arene Halogenation using the FAD-Dependent Halogenase RebH
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چکیده
منابع مشابه
Flavin redox chemistry precedes substrate chlorination during the reaction of the flavin-dependent halogenase RebH.
The flavin-dependent halogenase RebH catalyzes chlorination at the C7 position of tryptophan as the initial step in the biosynthesis of the chemotherapeutic agent rebeccamycin. The reaction requires reduced FADH(2) (provided by a partner flavin reductase), chloride ion, and oxygen as cosubstrates. Given the similarity of its sequence to those of flavoprotein monooxygenases and their common cosu...
متن کاملRobust in vitro activity of RebF and RebH, a two-component reductase/halogenase, generating 7-chlorotryptophan during rebeccamycin biosynthesis.
The indolocarbazole antitumor agent rebeccamycin is modified by chlorine atoms on each of two indole moieties of the aglycone scaffold. These halogens are incorporated during the initial step of its biosynthesis from conversion of L-Trp to 7-chlorotryptophan. Two genes in the biosynthetic cluster, rebF and rebH, are predicted to encode the flavin reductase and halogenase components of an FADH2-...
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The alpha-ketoglutarate-dependent hydroxylases and halogenases employ similar reaction mechanisms involving hydrogen-abstracting Fe(IV)-oxo (ferryl) intermediates. In the halogenases, the carboxylate residue from the His(2)(Asp/Glu)(1) "facial triad" of iron ligands found in the hydroxylases is replaced by alanine, and a halide ion (X(-)) coordinates at the vacated site. Halogenation is thought...
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This article reports an efficient CH activation process for regioselective halogenation of 1,4-benzodiazepinones. Direct halogenation with NXS (X = Br, I) affords halogenated benzodiazepinones on the central aromatic ring whereas catalyst (Pd(OAc)2) controlled CH activation furnishes regioselectively ortho halogenated benzodiazepinones on the phenyl side chain.
متن کاملDirected Evolution of RebH for Catalyst-Controlled Halogenation of Indole C-H Bonds.
RebH variants capable of chlorinating substituted indoles ortho-, meta-, and para- to the indole nitrogen were evolved by directly screening for altered selectivity on deuterium-substituted probe substrates using mass spectrometry. This systematic approach allowed for rapid accumulation of beneficial mutations using simple adaptive walks and should prove generally useful for altering and optimi...
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ژورنال
عنوان ژورنال: Angewandte Chemie
سال: 2013
ISSN: 0044-8249
DOI: 10.1002/ange.201300762