New Insights into the Conversion of Versicolorin A in the Biosynthesis of Aflatoxin B1.
A crucial and enigmatic step in the complex biosynthesis of aflatoxin B1 is the oxidative rearrangement of versicolorin A to demethylsterigmatocystin. This step is thought to proceed by an oxidation-reduction-oxidation sequence, in which the NADPH-dependent oxidoreductase AflM catalyzes the enclosed reduction step. AflM from Aspergillus parasiticus, after heterologous production in E. coli and purification, however, catalyzed the reduction of the hydroquinoid form of the starting compound versicolorin A (25% conversion) to a so far unknown product of aflatoxin biosynthesis. The asymmetric reduction of emodin hydroquinone to (R)-3,8,9,10-tetrahydroxy-6-methyl-3,4-dihydroanthracen-1(2H)-one (up to 82% for AflM) has also been observed in previous studies using MdpC from Aspergillus nidulans (monodictyphenone biosynthetic gene cluster). The first (nonenzymatic) reduction of emodin to emodin hydroquinone, for example with sodium dithionite, is obligatory for the enzymatic reduction by AflM or MdpC. These results imply an unprecedented role of AflM in the complex enzymatic network of aflatoxin biosynthesis.
Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg , Albertstr. 25, 79104 Freiburg, Germany.
David
D
Conradt
Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg , Albertstr. 25, 79104 Freiburg, Germany.
Michael A
MA
Schätzle
Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg , Albertstr. 25, 79104 Freiburg, Germany.
Julian
J
Haas
Department of Chemistry, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Craig A
CA
Townsend
Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg , Albertstr. 25, 79104 Freiburg, Germany.
Michael
M
Müller
D016604:Aflatoxin B1 / Q000096:biosynthesis* / Q000737:chemistry; D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*
D000880:Anthraquinones; D016604:Aflatoxin B1; C029826:versicolorin A; D009247:NADH, NADPH Oxidoreductases