title: Specific chlorination of isoquinolines by a fungal flavin-dependent halogenase.
abstract: Rdc2 is the first flavin-dependent halogenase identified from fungi. Based on the reported structure of the bacterial halogenase CmlS, 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 1a 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.
authors: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, USA.
authors: Jia
authors: J
authors: Zeng
authors: Anna K
authors: AK
authors: Lytle
authors: David
authors: D
authors: Gage
authors: Sean J
authors: SJ
authors: Johnson
authors: Jixun
authors: J
authors: Zhan
mesh_terms: D005415:Flavins / Q000737:chemistry* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D054879:Halogenation; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry* / Q000378:metabolism; D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D005415:Flavins; D005656:Fungal Proteins; D006843:Hydrocarbons, Chlorinated; D007546:Isoquinolines