FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus.
Verruculogen is a tremorgenic mycotoxin and contains an endoperoxide bond. In this study, we describe the cloning, overexpression and purification of a non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase FtmOx1 from Aspergillus fumigatus, which catalyses the conversion of fumitremorgin B to verruculogen by inserting an endoperoxide bond between two prenyl moieties. Incubation with (18)O(2)-enriched atmosphere demonstrated that both oxygen atoms of the endoperoxide bond are derived from one molecule of O(2). FtmOx1 is the first endoperoxide-forming non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase reported so far. A mechanism of FtmOx1-catalysed verruculogen formation is postulated and discussed.
Steffan
Nicola
N
Philipps-Universität Marburg, Institut für Pharmazeutische Biologie, Deutschhausstrasse 17A, D-35037, Marburg, Germany.
Grundmann
Alexander
A
Afiyatullov
Shamil
S
Ruan
Hanli
H
Li
Shu-Ming
SM
D001232:Aspergillus fumigatus / Q000201:enzymology*; D055162:Biocatalysis; D002851:Chromatography, High Pressure Liquid; D049308:Dioxygenases / Q000737:chemistry / Q000378:metabolism*; D006418:Heme; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism*; D010545:Peroxides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D007211:Indoles; D007656:Ketoglutaric Acids; D010545:Peroxides; C009658:verruculogen; D006418:Heme; D007501:Iron; D049308:Dioxygenases