Carvalho Ruby, Reid Ralph, Viswanathan Nina, Gramajo Hugo, Julien Bryan
Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, CA 94545, USA.
Gene. 2005 Oct 10;359:91-8. doi: 10.1016/j.gene.2005.06.003.
Disorazoles are polyketides produced by the myxobacterium Sorangium cellulosum So ce12. Their mode of action is to inhibit tubulin polymerization and destabilize microtubules. Using transposon mutagenesis, two mutant strains were identified that produced no disorazoles. Sequencing the DNA flanking the insertions revealed a polyketide synthase gene cluster that would encode three polypeptides, DszA, DszB, and DszC, with DszC containing both nonribosomal peptide synthetase and polyketide synthase modules. The disorazole polyketide synthase modules lack an acyltransferase domain. Instead, a separate gene, dszD, encodes an AT protein, thus revealing that the disorazole gene cluster falls into the trans-AT Type I family of PKS enzymes.
双吲哚茂类化合物是由粘细菌纤维堆囊菌So ce12产生的聚酮化合物。它们的作用方式是抑制微管蛋白聚合并使微管不稳定。利用转座子诱变，鉴定出两个不产生双吲哚茂类化合物的突变菌株。对插入位点侧翼的DNA进行测序，发现了一个聚酮合酶基因簇，该基因簇可编码三种多肽，即DszA、DszB和DszC，其中DszC同时含有非核糖体肽合成酶和聚酮合酶模块。双吲哚茂类聚酮合酶模块缺乏酰基转移酶结构域。相反，一个单独的基因dszD编码一种AT蛋白，从而表明双吲哚茂类基因簇属于PKS酶的反式-AT I型家族。
