New Insights into the Conversion of Versicolorin A in the Biosynthesis of Aflatoxin B1.
New Insights into the Conversion of Versicolorin A in the Biosynthesis of Aflatoxin B1.
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DOI：
10.1021/jacs.5b06770
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发表时间：
2015-09-02
影响因子：
15
通讯作者：
Müller M
中科院分区：
文献类型：
--
作者：
Conradt D;Schätzle MA;Haas J;Townsend CA;Müller M
在黄曲霉毒素B1复杂的生物合成过程中，一个关键而神秘的步骤是versicolorin A氧化重排为去甲基杂色曲霉素。该步骤被认为通过氧化-还原-氧化顺序进行，其中NADPH依赖性氧化还原酶AflM催化封闭的还原步骤。AflM来自寄生曲霉，在E.然而，大肠杆菌和纯化催化起始化合物versicolorin A的对苯二酚形式（25%转化率）还原成迄今未知的黄曲霉毒素生物合成产物。大黄素氢醌不对称还原为（R）-3，8，9，10-四羟基-6-甲基-3，4-二氢蒽-1（2 H）-酮（对于AflM高达82%）也已在使用来自构巢曲霉（Aspergillus nidulans）的MdpC的先前研究中观察到（单-网叶苯酮生物合成基因簇）。大黄素第一次（非酶促）还原为大黄素对苯二酚，例如用连二亚硫酸钠，对于通过AflM或MdpC的酶促还原是必须的。这些结果暗示了AflM在黄曲霉毒素生物合成的复杂酶网络中的前所未有的作用。
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 puriflcation, 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 (mono-dictyphenone biosynthetic gene cluster). The first (non-enzymatic) 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.