提奥斯特普顿成熟涉及去化-阿米迪化方法来处理C-终端甲基化骨干
1State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Journal of the American Chemical Society
|February 18, 2011
概括
这项研究揭示了一种新的脱精化-化途径在thioStrepton成熟. 这一过程产生终端胺,揭示了密码的C-终端甲基化在thiopeptide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
- 微生物学 微生物学
背景情况:
- 硫是一种复杂的,经过修改的,具有临床意义的类抗生素.
- 它们的生物合成涉及到一个保存的核心形成,但为个体成员提供独特的量身定制步骤.
研究的目的:
- 为了阐明在 thiopeptide 抗生素 thiostrepton 的成熟过程中不寻常的脱-化过程.
- 为了确定产生终端胺基部分所涉及的酶和中间体.
主要方法:
- 使用纯化蛋白 TsrB 和 TsrC 的酶分析.
- 在 thiostrepton 生物合成中的反应中间体的分析.
- 脱和化步骤的生物化学表征.
主要成果:
- 确定了TsrB作为一种催化甲基水解到碳酸盐中间体的碳酸乙烯酶催化剂.
- 证明TsrC,一种氨基转移酶,将碳酸盐转化为终端氨基酸.
- 揭示了前体的神秘C端甲基化.
结论:
- 这些发现揭示了一种新的脱-化途径,这对于列的最终结构至关重要.
- 这一途径突显出一种潜在的广泛机制,用于产生多种C-终端修饰 (,碳酸盐,胺) 在硫生物合成中.
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