立体選択的変換におけるリモネンエポキシードヒドロラーゼ変異体の触媒機構に関する構造的および計算的洞察
Zhoutong Sun1, Lian Wu2, Marco Bocola3,4
1Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , 32 West 7th Avenue, Tianjin Airport Economic Area, Tianjin 300308, China.
Journal of the American Chemical Society
|December 13, 2017
まとめ
誘導的進化により,選択反応のためのリモネンエポキシードヒドローラゼ (LEH) 変異体が生まれた. 計算と構造データは,なぜ変異体がサイクロヘクセン酸化物を効率的に処理するが,サイクロペンテン酸化物を処理しないかを明らかにする.
科学分野:
- 生物化学
- 酵素工学
- コンピュータ化学
背景:
- リモネンエポキシドヒドローラゼ (LEH) は,水解性脱対化反応において極めて重要です.
- (R,R) - と (S,S) - 選択性を有する突然変異を導いた.
研究 の 目的:
- LEH変異体の基質選択性のメカニズム的根拠を解明する.
- サイクロヘクセン酸化物を効率的に処理するが,サイクロペンテン酸化物を処理しない理由を理解する.
主な方法:
- LEHの指向的な進化
- 酵素基板複合体のX線結晶学
- 理論的な計算とアクティベーションエネルギーの計算
主要な成果:
- ミュータントは, (R,R) 製品と (S,S) 製品の両方に高いエナチオ選択性を示す.
- LEHの変種はサイクロヘクセン酸化物を効率的に変換しますが,サイクロペンテン酸化物はそうではありません.
- 計算分析により,結合ポケットの柔軟性により,サイクロペンテンの酸化反応における核フィール基板の配列が乱されていることが判明した.
結論:
- 酵素の柔軟性は基質の配列と反応結果に影響する.
- 構造とコンピューティングの洞察は 将来のタンパク質工学を様々な基板に導きます
- LEHメカニズムの理解は,選択的生物触媒の設計のための枠組みを提供します.
関連する概念動画
02:57Sharpless Epoxidation
5.2K
The conversion of allylic alcohols into epoxides using the chiral catalyst was discovered by K. Barry Sharpless and is known as Sharpless epoxidation. The use of a chiral catalyst enables the formation of one enantiomer of the product in excess. This chiral catalyst is mainly a chiral complex of titanium tetraisopropoxide and tartrate ester (specific stereoisomer). The stereoisomer used in the chiral catalyst dictates the formation of the enantiomer of the product. In other words, the use of...
5.2K
02:36Regioselectivity and Stereochemistry of Hydroboration
9.5K
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
9.5K
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
13.0K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
13.0K
02:24Acid-Catalyzed Ring-Opening of Epoxides
9.1K
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
9.1K
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
9.7K
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
9.7K
03:00Preparation of Epoxides
9.4K
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
9.4K