通过定向进化对生物催化 Baeyer-Villiger 反应产生传统电子效应
Guangyue Li1,2,3, Marc Garcia-Borràs4, Maximilian J L J Fürst5
1State Key Laboratory for Biology of Plant Diseases and Insect Pests/Key Laboratory of Control of Biological Hazard Factors (Plant Origin) for Agri-product Quality and Safety, Ministry of Agriculture , Institute of Plant Protection, Chinese Academy of Agricultural Sciences , Beijing 100081 , China.
Journal of the American Chemical Society
|July 26, 2018
概括
研究人员设计了贝耶-维利格单氧酶 (BVMOs) 来逆转化学反应中的区域选择性. 定向进化将酶偏好从正常转变为异常产物,为有机合成提供了新的控制.
科学领域:
- 有机化学
- 生物催化
- 蛋白质工程
背景情况:
- 在Baeyer-Villiger (BV) 反应中控制区域选择性是有机化学的一个持续挑战.
- 贝耶-维利格单氧酶 (BVMOs) 是能够催化BV反应的酶,但它们的区域选择性可能难以控制.
- 像m-CPBA这样的合成试剂对区域选择性提供有限的控制,通常只有利于正常产品.
研究的目的:
- 通过定向进化解决正常转换为异常的BVMO区域选择性的挑战.
- 设计一个热稳定的BVMO (TmCHMO) 来逆转线性子反应中的区域选择性.
- 调查观察到的区域选择性切换的机制基础.
主要方法:
- 代和突变发生在来自*Thermocrispum municipale* DSM 44069的热稳定BVMO (TmCHMO) 上.
- 使用4--2-butanone作为基质进行定向进化,以选择具有改变区域选择性的突变物.
- 使用动力参数,化温度,QM/MM和MD模拟来分析酶活性,稳定性和反应机制.
主要成果:
- 针对性进化将TmCHMO的区域选择性从99:1 (正常产品) 逆转为2:98 (异常产品) 对于4--2-butanone,而m-CPBA则无法做到这一点.
- 对于其他两种线性也观察到区域选择性的逆转.
- 突变物通常保留了催化活性和热稳定性, 表明蛋白质工程成功.
- 计算模拟显示,突变改变了中间体和过渡状态的构造,导致构造控制取代了区域选择性的电子控制.
结论:
- 定向进化是重编程BVMO区域选择性的强大工具,可合成异常的BV产物.
- 工程突变者表现出一种结构控制机制,
- 这些发现为未来的蛋白质工程工作提供了基础,用于设计针对不同合成应用的BVMOs.
相关概念视频
Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation
5.0K
Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by...
The carbonyl center is activated by...
5.0K
The Evidence for Evolution
48.3K
Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.
48.3K
Convergent Evolution
33.0K
Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
33.0K
Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction
2.8K
The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.
2.8K
Directing and Steric Effects in Disubstituted Benzene Derivatives
4.0K
When disubstituted benzenes undergo electrophilic substitution, the product distribution depends on the directing effect of both substituents. When the directing effects of both substituents reinforce each other, a single product is obtained. For example, bromination of p-nitrotoluene occurs ortho to the methyl group and meta to the nitro group, which is the same position, resulting in a single product. However, if the directing effects of the two groups oppose each other, the...
4.0K
π Electron Effects on Chemical Shift: Overview
1.7K
An applied magnetic field causes loosely bound π-electrons in organic molecules to circulate, producing a local or induced diamagnetic field over a large spatial volume. As the molecules tumble in solution, the field generated by π-electrons in spherical substituents results in a zero net field. However, the net field generated by π-electrons in non-spherical substituents is not zero. The effect of this induced field depends on the orientation of the molecule with respect to B0,...
1.7K


