The Aspergillus nidulans enzyme TdiB catalyzes prenyltransfer to the precursor of bioactive asterriquinones.
The asterriquinones represent a class of ascomycete metabolic products whose significance stems from remarkable and useful pharmacological activities, among those antiretroviral (e.g., against the HI-virus), antitumor, and antidiabetes properties. Recently, the first genetic locus for an asterriquinone, the clustered terrequinone genes tdiA-E, was identified during a genome-wide screen in Aspergillus nidulans for "orphan" natural product biosynthesis loci. Here, we describe overexpression and characterization of TdiB, which catalyzes the reverse prenylation event during terrequinone A biosynthesis, which is the transfer of dimethylallyl diphosphate to carbon atom 2' of the intermediate didemethylasterriquinone D, to yield asterriquinone C-1. TdiB does not depend on the presence of divalent metal cations for catalysis and lacks the canonical prenyl diphosphate binding motif (D/N)DXXD.
Schneider
Patrick
P
Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany.
Weber
Monika
M
Hoffmeister
Dirk
D
D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D013058:Mass Spectrometry; D015394:Molecular Structure; D009154:Mutation; D017422:Sequence Analysis, DNA
D005656:Fungal Proteins; D007211:Indoles; C496935:terrequinone A; C035746:asterriquinone; D004122:Dimethylallyltranstransferase