Chemical Biology Department, Advanced Science Institute, RIKEN, Wako, Saitama, Japan.
Chembiochem. 2011 Jun 14;12(9):1376-82. doi: 10.1002/cbic.201000672. Epub 2011 May 23.
Aspergillus oryzae is a fungus widely used in traditional Japanese fermentation industries. Its inability to produce mycotoxins, due to mutation or transcriptional repression of the genes responsible for their biosynthesis, is consistent with the hypothesis that A. oryzae is a domesticated species derived from A. flavus, a wild species that is a well-known producer of aflatoxin. In contrast, the cyclopiazonic acid (CPA) biosynthetic gene (cpa) cluster in A. oryzae contains genes that have been lost in A. flavus. Through targeted gene inactivation, isolation of the corresponding metabolite, and evaluation of biological activity of the metabolite, we demonstrated that an A. oryzae-specific gene-cpaH-mediates the conversion of CPA into the less toxic 2-oxocyclopiazonic acid, a new analogue of CPA. The detoxifying properties of cpaH, which have been lost in the A. flavus pathway, reflect the relationship of the two species.
米曲霉是一种广泛应用于日本传统发酵工业的真菌。由于负责其生物合成的基因发生突变或转录抑制，米曲霉无法产生真菌毒素，这与米曲霉是由黄曲霉（一种已知的黄曲霉毒素产生菌）驯化而来的假说一致。相比之下，米曲霉中环匹阿尼酸（CPA）生物合成基因（cpa）簇中存在一些在黄曲霉中丢失的基因。通过靶向基因失活、分离相应的代谢产物以及对代谢产物的生物活性进行评估，我们证明了一个米曲霉特异性基因 cpaH 介导了 CPA 向毒性较低的 2-氧环匹阿尼酸的转化，这是 CPA 的一种新类似物。cpaH 在黄曲霉途径中丢失的解毒特性反映了这两个物种的关系。
