甲基因组挖掘揭示了聚胺胺作为翻译后修饰的核糖体
Michael F Freeman1, Cristian Gurgui, Maximilian J Helf
1Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
Science (New York, N.Y.)
|September 18, 2012
概括
这项研究揭示了海洋海绵毒素是由细菌通过核糖体合成的,这挑战了核糖体产品中只有l-氨基酸的范式. 这些毒素作为强大的单分子离子通道起作用.
科学领域:
- 生物化学和分子生物学
- 自然产品化学 自然产品化学
- 海洋生物学 海洋生物学
背景情况:
- 现行范式指出,通过核糖体合成的和蛋白质仅包含l-氨基酸.
- 海洋海绵衍生的聚胺胺是具有复杂结构的强有力的天然产品毒素.
- 这种复杂的自然产品的生物合成途径往往难以阐明.
研究的目的:
- 为了研究海洋海绵衍生的聚氨胺的生物合成起源.
- 识别和描述负责这些毒素的翻译后修饰的酶.
- 了解作为离子通道的聚胺胺的功能机制.
主要方法:
- 从海洋海绵元基因组中分离生物合成基因.
- 生物信息分析以确定参与翻译后修改的候选酶.
- 候选酶的功能验证,包括一个激进的S-adenosylmethionine酶.
主要成果:
- 聚胺胺的生物合成基因表现出一种细菌基因结构.
- 对48个翻译后修改的6个候选酶被确定,包括广泛的表皮化和甲基化.
- 一种激进的S-adenosylmethionine酶被证实可催化多种氨基酸的单向表皮化.
结论:
- 聚胺胺是通过核糖体合成的,这挑战了在核糖体产品中L-氨基酸的独家使用.
- 复杂的翻译后修改,包括表皮化和甲基化,对于毒素的功能至关重要.
- 这些发现扩大了已知的核糖体系统的生物合成能力,并为生物工程提供了途径.
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