埃尼迪恩抗瘤抗生素maduropeptin生物合成具有C-甲基转移酶,它作用于与CoA结合的芳香基质
Jianya Ling1, Geoffrey P Horsman, Sheng-Xiong Huang
1Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Journal of the American Chemical Society
|August 20, 2010
概括
马杜罗佩普丁 (MDP) 抗生素的生物合成
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 自然产品 化学 化学
背景情况:
- 马杜罗佩普丁 (MDP) 是一种由Actinomadura madurae生产的抗瘤抗生素.
- MDP的染色体含有3,6-二甲基酸部分.
- 了解MDP生物合成可以为新抗癌药物的开发提供信息.
研究的目的:
- 为了阐明maduropeptin的3,6-二甲基酸部分的生物合成途径.
- 描述MdpB,MdpB1,MdpB2和MdpB3酶在这一途径中的作用.
- 为了研究MDP芳香酸生物合成中使用的不寻常的酶逻辑.
主要方法:
- 对MDP生物合成基因集群的生物信息分析.
- 酶性测试以确定基质特异性和反应机制.
- 对MdpB1和MdpB2酶的生物化学表征.
主要成果:
- 芳香酸生物合成途径的MDP具有一个意想不到的序列的酶步骤.
- 通过CoA结合,MdpB2通过CoA结合激活酸类型.
- 在MdpB2催化激活之前,MdpB1独特地C-甲基化了一种与CoA结合的芳香酸.
结论:
- MDP染色体的芳香酸部分的生物合成遵循一种非常规的酶序列.
- MdpB1的C-甲基化CoA结合基质的能力是新鲜的.
- MdpB2的散乱的CoA结合酶活性为设计新型MDP类似物提供了潜力.
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