School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
J Am Chem Soc. 2011 Oct 19;133(41):16635-41. doi: 10.1021/ja206914q. Epub 2011 Sep 26.
The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.
迭代高度还原聚酮合酶的编程机制仍然是次生代谢物未解决的关键问题之一。我们在编码紧密相关化合物天兰素和去甲贝色汀生物合成的聚酮合酶之间进行了合理的结构域交换。在米曲霉中表达杂交合酶导致了重编程化合物的产生，其中甲基化模式和链长的变化可以映射到结构域交换。这些实验首次揭示了这些系统中编程的起源。结构域交换结合来自天兰素生物合成基因簇的两个细胞色素 P450 编码基因的共表达，导致了已灭绝代谢物贝色汀的复活。
