Specific chlorination of isoquinolines by a fungal flavin-dependent halogenase

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Zeng, Jia¹  Lytle, Anna K.²  Gage, David¹  Johnson, Sean J.²  Zhan, Jixun¹ 

[1] Utah State Univ, Dept Biol Engn, Logan, UT 84322 USA

[2] Utah State Univ, Dept Chem & Biochem, Logan, UT 84322 USA

关键词: Fungal halogenase;    Flavin-dependent;    Homology model;    Isoquinolines;    Substrate specificity;   

DOI  :  10.1016/j.bmcl.2012.12.038

来源: Elsevier

【 摘 要 】

Rdc2 is the first flavin-dependent halogenase identified from fungi. Based on the reported structure of the bacterial halogenase Cm1S, we have built a homology model for Rdc2. The model suggests an open substrate binding site that is capable of binding the natural substrate, monocillin II, and possibly other molecules such as 4-hydroxyisoquinoline (1) and 6-hydroxyisoquinoline (2). In vitro and in vivo halogenation experiments confirmed that 1 and 2 can be halogenated at the position ortho to the hydroxyl group, leading to the synthesis of the chlorinated isoquinolines la and 2a, respectively, which further expands the spectrum of identified substrates of Rdc2. This work revealed that Rdc2 is a useful biocatalyst for the synthesis of various halogenated compounds. (C) 2012 Elsevier Ltd. All rights reserved.

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