通过硫酸盐消除形成酶性亚齐里丁的分子基础
Sumire Kurosawa1, Fumihito Hasebe1, Hironori Okamura1
1Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Journal of the American Chemical Society
|August 23, 2022
概括
研究人员阐明了天然产品中阿齐里丁环的生物合成. 发现了一种涉及硫酸盐消除的新型酶机制,为阿齐里丁环形成提供了第一个分子洞察力.
科学领域:
- 生物化学
- 有机化学
- 分子生物学
背景情况:
- 通过其阿齐里丁环的DNA化,自然产物如米托米C和阿齐诺米B具有抗瘤特性.
- 这些化合物的亚齐里丁环形成的生物合成途径在很大程度上是未知的.
研究的目的:
- 研究瓦扎比提德A中的亚齐里丁环的生物合成,该化合物与亚齐诺米辛B结构相关.
- 阐明阿齐里丁环形成的酶机制和分子基础.
主要方法:
- 研究了vazabitide A的生物合成,确定Vzb10/11是通过硫酸盐排泄导致阿齐里丁环形成的酶.
- 试图结晶Vzb10/11和同源酶AziU3 / U2从阿兹诺米辛B生物合成.
- 确定了AziU3/U2的晶体结构,揭示了一个新的蛋白质折叠.
主要成果:
- 确定Vzb10/11作为一种通过硫酸盐分离催化阿齐里丁环形成的新型酶.
- AziU3/U2 的晶体结构显示出一种独特的蛋白质折叠.
- 结构分析显示酶优化基质构成并增强氨基群核友性,形成类似SN2的阿齐里丁环.
结论:
- 这项研究提供了天然产品生物合成中阿齐里丁环形成的第一个分子理解.
- 鉴定到的酶机制为含有亚齐里丁的生物活性分子的合成提供了见解.
相关概念视频
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