New Insights into the Conversion of Versicolorin A in the Biosynthesis of Aflatoxin B1

详细信息    查看全文

• 作者：David Conradt ; Michael A. Sch盲tzle ; Julian Haas ; Craig A. Townsend ; Michael M眉ller
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：September 2, 2015
• 年：2015
• 卷：137
• 期：34
• 页码：10867-10869
• 全文大小：256K
• ISSN：1520-5126

文摘

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鈥搑eduction鈥搊xidation 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.