設計酵素におけるボロン触媒
Lars Longwitz1, Reuben B Leveson-Gower1, Henriëtte J Rozeboom2
1Stratingh Institute for Chemistry, University of Groningen, Groningen, The Netherlands.
Nature
|May 8, 2024
まとめ
科学者は遺伝子コードの拡張を用いて 新しい設計酵素を作り出しました この酵素は,ボロン酸の部分を含み,新しい化学反応を可能にし,様々な基質に対する高いエナチオ選択性を達成します.
科学分野:
- 生物化学
- 合成生物学
- 有機化学
背景:
- 酵素は持続可能な化学生産に不可欠ですが,反応機構は限られています.
- 酵素の機能を拡張するには 非生物学的機能を組み込む必要があります
- 現在の生物触媒は 自然な酵素反応の狭い範囲によって制限されています
研究 の 目的:
- 遺伝的にコードされた酵素を 作り出すために
- 自然の範囲を超えた 反応を可能にする 設計酵素を開発する
- プログラム可能な生物触媒の遺伝子コード拡張の可能性を実証する.
主な方法:
- ボロン酸をタンパク質に組み込む 遺伝子コードの拡張
- 酵素の活性と選択性を高めるための進化を導いた.
- 構造的および機械的分析のためのX線結晶学,HRMS,および11B NMRスペクトロスコーピー.
主要な成果:
- ボロン酸を含む新しい酵素が成功して合成され,遺伝子コード化されました.
- この酵素は,オキシーム形成を通じて,ヒドロキシケトンの運動解消を触媒化した.
- 誘導的な進化により,天然の酵素のようなエナチオ選択性を持つ変種が生まれた.
- 酵素の独特の活性化モードは 構造的およびスペクトル学的に確認された.
結論:
- 遺伝子コードの拡張により,異種生物の触媒群を持つ設計酵素が作られます.
- ボロンを含む酵素は,天然の酵素では達成できない新しい反応機構にアクセスできます.
- このアプローチは,エナチオ選択的生物触媒とプログラム可能な酵素設計のための新しい道を開きます.
関連する概念動画
Introduction to Mechanisms of Enzyme Catalysis
8.1K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
8.1K
Catalytically Perfect Enzymes
4.0K
The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
Most enzymes...
Most enzymes...
4.0K
Enzymes
81.5K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
81.5K
Hydroboration-Oxidation of Alkenes
8.1K
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
8.1K
Regioselectivity and Stereochemistry of Hydroboration
8.1K
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...
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...
8.1K
Induced-fit Model
80.8K
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
80.8K


