Bradshaw Rosie E, Jin Hongping, Morgan Branwen S, Schwelm Arne, Teddy Olivia R, Young Carolyn A, Zhang Shuguang
National Centre for Advanced Bio-Protection Technologies, Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand.
Mycopathologia. 2006 May;161(5):283-94. doi: 10.1007/s11046-006-0240-5.
Dothistromin is a polyketide toxin, produced by a fungal forest pathogen, with structural similarity to the aflatoxin precursor versicolorin B. Biochemical and genetic studies suggested that there are common steps in the biosynthetic pathways for these metabolites and showed similarities between some of the genes. A polyketide synthase gene (pksA) was isolated from dothistromin-producing Dothistroma septosporum by hybridization with an aflatoxin ortholog from Aspergillus parasiticus. Inactivation of this gene in D. septosporum resulted in mutants that could not produce dothistromin but that could convert exogenous aflatoxin precursors, including norsolorinic acid, into dothistromin. The mutants also had reduced asexual sporulation compared to the wild type. So far four other genes are known to be clustered immediately alongside pksA. Three of these (cypA, moxA, avfA) are predicted to be orthologs of aflatoxin biosynthetic genes. The other gene (epoA), located between avfA and moxA, is predicted to encode an epoxide hydrolase, for which there is no homolog in either the aflatoxin or sterigmatocystin gene clusters. The pksA gene is located on a small chromosome of approximately 1.3 Mb in size, along with the dothistromin ketoreductase (dotA) gene.
多胝霉素是一种聚酮化合物毒素，由一种真菌森林病原体产生，其结构与黄曲霉毒素前体杂色曲霉素B相似。生化和遗传学研究表明，这些代谢产物的生物合成途径存在共同步骤，并且一些基因之间存在相似性。通过与寄生曲霉的黄曲霉毒素直系同源基因杂交，从产生多胝霉素的多隔多胝菌中分离出一个聚酮合酶基因（pksA）。该基因在多隔多胝菌中失活导致突变体无法产生多胝霉素，但能够将包括去甲赭曲霉素在内的外源黄曲霉毒素前体转化为多胝霉素。与野生型相比，这些突变体的无性孢子形成也有所减少。到目前为止，已知还有其他四个基因紧邻pksA成簇排列。其中三个基因（cypA、moxA、avfA）预计是黄曲霉毒素生物合成基因的直系同源基因。另一个基因（epoA）位于avfA和moxA之间，预计编码一种环氧化物水解酶，在黄曲霉毒素或柄曲霉素基因簇中均无同源物。pksA基因位于一条大小约为1.3 Mb的小染色体上，与多胝霉素酮还原酶（dotA）基因在一起。
