A1和B1纳皮胺的总酶合成
Shaun M K McKinnie1, Zachary D Miles1, Peter A Jordan1
1Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego , La Jolla , California 92093 , United States.
Journal of the American Chemical Society
|December 12, 2018
概括
纳皮胺生物合成途径现在已经完全阐明,揭示了五种酶如何产生这些复杂的抗菌甲基. 这一发现使有效的化学酶合成有价值的化天然产品成为可能.
科学领域:
- 自然产品生物合成
- 酵素学
- 有机化学
背景情况:
- 纳皮胺是具有抗菌性和细胞毒性特性的细菌甲胺.
- 它们的生物合成基因群在11年前被发现,
研究的目的:
- 为了充分阐明纳皮胺的生物合成途径.
- 描述纳皮胺生产中的初始和最终的酶步骤.
- 开发一种合成纳皮胺酶的化学酶方法.
主要方法:
- 关键酶的表征:NapT9 (芳转移酶) 和NapH4 (依赖瓦纳的氧化酶同类物).
- 使用复合酶进行体外合成.
- 一个化酶合成.
主要成果:
- 完整的生物合成途径涉及三种基质和五种酶.
- NapH4催化了一种独特的诱导循环,形成两个立体中心.
- 纳普H1具有双重活性,催化化和化.
- 通过化学酶方法在一天内合成了数毫克的纳皮拉迪奥米辛B1.
结论:
- 精简的纳皮胺生物合成展示了依赖瓦纳的氧化酶酶的力量.
- 开发的化学酶方法为复杂的化天然产品提供了可行的合成途径.
- 这项工作为生产以前化学上无法获得的天然产品铺平了道路.
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