Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis
Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis
复制标题
阿齐霉素 B 生物合成基因簇的表征揭示了用于萘甲酸酯生物合成的不同迭代 I 型聚酮合酶
DOI：
10.1016/j.chembiol.2008.05.021
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发表时间：
2008-07-21
影响因子：
--
通讯作者：
Liu, Wen
中科院分区：
文献类型：
--
作者：
Zhao, Qunfei;He, Qingli;Liu, Wen
阿嗪霉素B是一种复杂的天然产物，含有密集组装的功能，具有强大的抗肿瘤活性。azi基因簇的克隆和序列分析揭示了一个迭代I型聚酮合酶（PKS）基因，五个非核糖体肽合成酶（NRPS）基因和许多基因编码的生物合成的不寻常的积木和剪裁步骤azinomycin B生产。AziB作为5-甲基-萘甲酸（NP）合酶的表征显示了由细菌迭代I型PKS控制的芳香族聚酮生物合成中的独特选择性还原模式。杂环表达建立了从5-甲基-NPA到第一个结构单元3-甲氧基-5-甲基-NPA的PKS-后修饰路线。提出的azinomycin B生物合成途径为研究构建结构独特和药学上重要的基团的酶促机制奠定了基础，包括前所未有的氮杂双环系统和高活性的环氧化物部分。
Azinomycin B is a complex natural product containing densely assembled functionalities with potent antitumor activity. Cloning and sequence analysis of the azi gene cluster revealed an iterative type I polyketide synthase (PKS) gene, five nonribosomal peptide synthetases (NRPSs) genes and numerous genes encoding the biosynthesis of unusual building blocks and tailoring steps for azinomycin B production. Characterization of AziB as a 5-methyl-naphthoic acid (NP) synthase showed a distinct selective reduction pattern in aromatic polyketide biosynthesis governed by bacterial iterative type I PKSs. Heterologous expression established the PKS-post modification route from 5-methyl-NPA to reach the first building block 3-methoxy-5-methyl-NPA. This proposed azinomycin B biosynthetic pathway sets the stage to investigate the enzymatic mechanisms for building structurally unique and pharmaceutically important groups, including the unprecedented azabicyclic ring system and highly active epoxide moiety.