无辅助因子氧化酶指导 antraquinone-fused enediyne 的生物合成
Chun Gui1, Edward Kalkreuter1, Yu-Chen Liu1
1Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, USA.
Nature chemical biology
|November 9, 2023
概括
两种新的无辅助因子氧化酶,TnmJ和TnmK2,催化了基F环裁步骤在基融合基因 (AFE) 生物合成. 这些酶使关键的变形,环氧化和氧化环分裂反应成为可能.
科学领域:
- 自然产品生物合成 自然产品生物合成
- 酶催化酶的催化作用
- 有机化学 有机化学
背景情况:
- 氨基融合氨基 (AFEs) 是细胞毒性分子,具有十个成员的氨基核心和氨基部分.
- AFE循环过程涉及F环环氧化物形成,这是一个具有显著结构多样性的区域.
- 之前对丁氨酸A的研究发现了环氧化物安装方面的挑战,并且在其生物合成基因集群中缺乏已识别的氧化酶.
研究的目的:
- 为了确定负责F环量身定制的酶在tiancimycin生物合成.
- 阐明这些新型酶的催化机制.
- 扩大对自然产品生物合成中的无因子氧化酶功能的理解.
主要方法:
- 比较基因组学以确定tnm生物合成基因集群中的候选酶.
- 纯化酶的生物化学表征.
- 酶基质相互作用的结构分析.
主要成果:
- 鉴定两个连续作用的无因子氧化酶,TnmJ (甲基转移酶折叠) 和TnmK2 (α/β-酸酶折叠).
- 证明TnmJ和TnmK2催化了AFE F环的变形,环氧化和氧化环裂变.
- 证据表明,AFE中素部分有助于在没有外源辅助因子的情况下催化这些反应.
结论:
- TnmJ和TnmK2对于AFEF环量身定制在天胺蛋白生物合成中至关重要.
- 这些酶代表了一个被低估的无因子氧化酶家族.
- 这些发现填补了AFE生物合成和无辅助因子酶机制的重大知识差距.
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