克罗托纳酶催化能够灵活地产生功能化的普罗林和卡巴胺
Refaat B Hamed1, Luc Henry, J Ruben Gomez-Castellanos
1Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Journal of the American Chemical Society
|November 19, 2011
概括
工程酶可以产生功能化的烯衍生物和双循环β-乳酸盐. 这种生物催化剂推进了立体选择性合成,并产生具有四元中心的复杂分子.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 有机合成 有机合成
- 药物化学 药物化学
背景情况:
- 碳氧甲基林合成酶 (CMPSs) 是参与自然产品生物合成的酶.
- 工程CMPS可以扩大其基质范围和催化能力.
- 双循环β-乳酸盐是药品中重要的结构动图.
研究的目的:
- 为了证明野生型和工程CMPSs的生物催化多功能性.
- 用于制备功能化的5 - 碳素甲基林衍生物.
- 为了将这些衍生物转化为新型双循环β-乳酸盐.
主要方法:
- 利用了野生型和工程化碳氧甲基烯合成酶 (CMPSs).
- 采用氨基酸化物和马洛尼尔-协酶A作为基质.
- 使用卡巴胺合成酶将得到的烯衍生物转化为双循环β-乳酸盐.
主要成果:
- 已制备的功能化5-碳素甲基烯衍生物,在各种环状位置甲基化.
- 通过使用工程CMPS实现了四元中心在C-2或C-5的化合物的立体选择合成.
- 从烯衍生物中成功合成了新型双循环β-乳酸盐.
结论:
- 克罗托纳酶超级家族的酶对立体选择性生物催化有价值.
- 碳烯生物合成途径可以被设计为新型的双循环β-乳酸生产.
- 工程生物催化剂显示出创造具有四元中心的复杂分子的潜力.
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