在循环氨基酸生物合成过程中,由非海姆铁酶进行神秘化
Frédéric H Vaillancourt1, Ellen Yeh, David A Vosburg
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|August 27, 2005
概括
研究人员发现了新的酶,CmaB和CmaC,生物化和循环化合物. 这一发现揭示了在天然产品生物合成中形成环环的新机制.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 自然产品生物合成 自然产品生物合成
背景情况:
- 在生物合成过程中,超过4000种天然产品包含素 (,,).
- 化显著影响这些天然产品的生物活性.
- 催化未激活的阿里法基的化酶仍然没有表征.
研究的目的:
- 描述参与冠胺酸 (CMA) 生物合成的新型酶.
- 在CMA合成中阐明环环形成的机制.
- 确定第一个已知的原酶酶,它对未被激活的阿利法基产生作用.
主要方法:
- 研究了来自Pseudomonas注射器的五种蛋白质 (CmaA,CmaB,CmaC,CmaD,CmaE) 的活性.
- 利用生物化学分析来确定CMA构造中的酶功能.
- 描述了CmaB作为非海姆Fe2+),阿尔法-甲酸依赖酶和CmaC作为环烯形成酶.
主要成果:
- 确定了CmaB作为其类中第一个表现出酶活性的酶,特别是在玛位置化l-allo-isoleucine.
- 证明CmaC可催化马化中间体从马化中间体形成环烯基环.
- 确定CmaB和CmaC的作用是连续的:马化,然后是分子内马消除.
结论:
- CmaB和CmaC的联合作用代表了一种新的生物策略,通过化和消除来形成环的环.
- 这项研究描述了以前未知的酶,并扩大了对酶多样性和功能的理解.
- 这些发现提供了关于植物毒素如冠状腺素的生物合成的见解.
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