Biosynthesis of the antitumor chromomycin A3 in Streptomyces griseus:: Analysis of the gene cluster and rational design of novel chromomycin analogs
Biosynthesis of the antitumor chromomycin A3 in Streptomyces griseus:: Analysis of the gene cluster and rational design of novel chromomycin analogs
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DOI：
10.1016/j.chembiol.2003.12.011
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
Méndez, C
中科院分区：
文献类型：
--
作者：
Menéndez, N;Nur-e-Alam, M;Méndez, C
金黄色葡萄球菌抗癌药物色霉素A(3)的生物合成基因簇。灰霉菌已被鉴定和鉴定。它全长43kb，包含36个基因，涉及聚酮的生物合成和修饰、脱氧糖的生物合成和糖的转移、途径调节和抗性。该簇的组织结构明显不同于与之密切相关的米特拉霉素。该簇参与了色霉素A(3)的生物合成，通过破坏编码参与侧链还原的聚酮还原酶的cmmWI基因而被证明。合成了三个具有抗肿瘤活性的新型色霉素衍生物，分别命名为色霉素SK、色霉素SA和色霉素SDK，它们的3-侧链不同。提出了一种生物合成色霉素A(3)及其脱氧糖的途径。
The biosynthetic gene cluster of the aureolic acid type antitumor drug chromomycin A(3) from S. griseus subsp. griseus has been identified and characterized. It spans 43 kb and contains 36 genes involved in polyketide biosynthesis and modification, deoxysugar biosynthesis and sugar transfer, pathway regulation and resistance. The organization of the cluster clearly differs from that of the closely related mithramycin. Involvement of the cluster in chromomycin A(3) biosynthesis was demonstrated by disrupting the cmmWI gene encoding a polyketide reductase involved in side chain reduction. Three novel chromomycin derivatives were obtained, named chromomycin SK, chromomycin SA, and chromomycin SDK, which show antitumor activity and differ with respect to their 3-side chains. A pathway for the biosynthesis of chromomycin A(3) and its deoxysugars is proposed.