Engineering anthracycline biosynthesis toward angucyclines
Engineering anthracycline biosynthesis toward angucyclines
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DOI：
10.1128/aac.47.4.1291-1296.2003
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发表时间：
2003-04-01
影响因子：
4.9
通讯作者：
Mäntsälä, P
中科院分区：
文献类型：
--
作者：
Metsä-Ketelä, M;Palmu, K;Mäntsälä, P
通过使用从沉默的抗生素生物合成基因簇中分离出的安古环素特异性环化酶 pgaF，将两种蒽环类抗生素诺加霉素和阿克拉霉素的生物合成途径针对安古环素。将 pgaF 添加到包含诺加霉素早期生物合成基因的基因盒中，导致产生两种已知的安古环酮代谢物：雷贝霉素及其前体 UWM6。 pgaF 的底物灵活性通过用等效的阿克拉霉素基因以及 aknE2 和 aknF 替换基因盒中的诺加霉素最小聚酮化合物合酶基因来证明，这些基因指定了阿克拉霉素生物合成中不寻常的丙酸起始单元。这种修饰导致产生了一种新型安古环酮 MM2002，其中预期的乙基侧链被纳入第四个环中。
The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin and its precursor, UWM6. Substrate flexibility of pgaF was demonstrated by replacement of the nogalamycin minimal polyketide synthase genes in the gene cassette with the equivalent aclacinomycin genes together with aknE2 and aknF, which specify the unusual propionate starter unit in aclacinomycin biosynthesis. This modification led to the production of a novel angucyclinone, MM2002, in which the expected ethyl side chain was incorporated into the fourth ring.