胺二酸盐依赖的JanthE的工程用于三级酒精的合成
Lucrezia Lanza1, Daniela Bjarnesen1, Mehmet Mervan Cakar2
1University of Freiburg: Albert-Ludwigs-Universitat Freiburg, Institute of Pharmaceutical Sciences, GERMANY.
研究人员设计了一种依赖胺二酸盐的酶JanthE,以改善性三级酒精合成. 一个关键的变体显著促进了对固态阻碍化合物的产品形成,使得制剂规模生产成为可能.
科学领域:
- 生物催化剂是一种生物催化剂.
- 酶工程是什么? 酶工程是什么?
- 有机合成 有机合成
背景情况:
- 吉拉性三级醇,特别是那些有庞大的群体的酶选择性合成,仍然是有机化学中的一个重大挑战.
- 胺二酸盐依赖的酶提供了一个有前途的途径,但低产量往往限制了它们的应用.
- JanthE酶显示了化 - 基交叉合的潜力,但需要优化以实现高效生产.
研究的目的:
- 为了提高JanthE酶的催化效率和产品产量,用于合成固态阻碍的性三级酒精.
- 研究蛋白质工程策略,以提高JanthE在复杂合成反应中的性能.
- 为了证明工程JanthE变体的制备规模适用性.
主要方法:
- 在使用2-oxobutanoate和phenoxy-2-propanone的模型反应中研究了JanthE的性能.
- 采用了基于对接实验的合理蛋白质工程,以确定关键活性部位残留物.
- 生成和特征的单点 (K567S) 和双点 (Y297P_K567S) JanthE变种.
主要成果:
- 单点变体JanthE K567S表现出产品形成的五倍增长,具有高反选择性 (90% ee).
- 双点变体Y297P_K567S表现出与更长的基板产品形成的类似五倍增加.
- 工程酶变种使得制剂规模的合成成为可能,证实了实际应用.
结论:
- 理性蛋白质工程有效地提高了JanthE的性能,用于合成固态阻碍的三级酒精.
- JanthE显示出显著的可变性和多功能性,为更广泛的生物催化应用铺平了道路.
- 优化的JanthE变体为有价值的性酒精的酶选择性合成提供了可行的方法.
更多相关视频
10:12Retropinacol/Cross-pinacol Coupling Reactions - A Catalytic Access to 1,2-Unsymmetrical Diols
Published on: April 4, 2014
10:42Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
相关概念视频
Aldol Condensation with β-Diesters: Knoevenagel Condensation
Preparation of Alcohols via Addition Reactions
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
Ethers from Alcohols: Alcohol Dehydration and Williamson Ether Synthesis
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.
Acid-Catalyzed Dehydration of Alcohols to Alkenes
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Preparation of Alcohols via Substitution Reactions
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group.ÃÂÃÂ The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2,ÃÂÃÂ depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from...
