エーテル・クロスリンク・フォーミング・ラジカルSAM酵素における基板制御による触媒
Journal of the American Chemical Society
|September 28, 2023
まとめ
ラジカルS-アデノシルメチオニン (rSAM) 酵素はドロバクチンのような抗生物質にユニークなクロスリンクを導入します. この研究は,これらの酵素が多機能で,エーテルとC-Cクロスリンク形成を制御する基板モチーフを持つことを明らかにしています.
科学分野:
- 生物化学
- 自然製品の生物合成
- 酵素学
背景:
- ダロバクチンは複雑なヘプタペプチド抗生物質です.
- それはエーテルとC-Cのクロスリンクの両方を特徴としています.
- 原因となる酵素 DarE は,S-アデノシルメチオニン (rSAM) 酵素ですが,この2つのクロスリンクがどのように形成されるかは不明です.
研究 の 目的:
- ダロバクチンのような RiPP (リボソーム合成および翻訳後の改変ペプチド) の生物合成経路を調査する.
- rSAM酵素によるクロスリンク形成の基礎となる酵素機構を理解する.
- 新しいダロペプチドを発見し,その構造的多様性を制御する要因を解明する.
主な方法:
- 生物合成遺伝子クラスター分析
- マチューラーゼ酵素の遺伝子解析
- ダロペプチドマチュラゼにおける主要残基のサイト指向型変異.
- 酵素活動の生化学的特徴
主要な成果:
- エーテルクロスリンクのみを含む2つの新しいダロペプチドの識別と特徴付け.
- ダロペプチドマチュラゼが固有の多機能性を有することを示した.
- 基板特異的なモチーフがエーテルクロスリンク,C-Cクロスリンク,およびセル酸化の形成を決定する証拠.
- rSAM酵素は,基板の認識に基づく異なる化学変換を触媒化することができます.
結論:
- ダロペプチド成熟酵素は,多種多様な翻訳後の改変を触媒にすることができる多機能酵素である.
- サブストラット配列は,rSAM酵素活性の化学的結果に直接影響する.
- この研究は,新しいRiPPを発見し,rSAM酵素の多機能性の規制を理解するための枠組みを提供します.
さらに関連する動画
11:17Synthesis of Programmable Main-chain Liquid-crystalline Elastomers Using a Two-stage Thiol-acrylate Reaction
Published on: January 19, 2016
21.8K
06:49Atom Transfer Radical Polymerization of Functionalized Vinyl Monomers Using Perylene as a Visible Light Photocatalyst
Published on: April 22, 2016
11.9K
関連する概念動画
02:26Base-Catalyzed Ring-Opening of Epoxides
8.6K
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
8.6K
02:35Free-Radical Chain Reaction and Polymerization of Alkenes
7.9K
The conversion of alkenes to macromolecules called polymers is a reaction of high commercial importance. The structure of the polymer is defined by a repeating unit, while the terminal groups are considered insignificant. The average degree of polymerization represents the number of repeating units in the polymer molecule and is denoted by the subscript n.
7.9K
01:02Radical Reactivity: Electrophilic Radicals
1.9K
Radicals adjacent to electron‐withdrawing groups are called electrophilic radicals. These radicals readily react with nucleophilic alkenes. For example, the malonate radical, in which the radical center is flanked by two electron‐withdrawing groups, reacts readily with butyl vinyl ether, which consists of an electron‐donating oxygen substituent. The reaction between electrophilic malonate radical and nucleophilic vinyl ether is favored because the radical has a...
1.9K
02:45E2 Reaction: Kinetics and Mechanism
10.4K
SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, it functions as a strong base and abstracts a beta hydrogen in the E2 mechanism. The rate-limiting transition state in E2 elimination reactions is characterized by partially broken carbon–hydrogen and carbon–halogen bonds and a partially formed pi bond between the alpha and beta carbons. The beta hydrogen and halide are eliminated...
10.4K
01:11Radical Reactivity: Overview
2.1K
Radicals, the highly reactive species, gain stability by undergoing three different reactions. The first reaction involves a radical-radical coupling, in which a radical combines with another radical, forming a spin‐paired molecule. The second reaction is between a radical and a spin‐paired molecule, generating a new radical and a new spin‐paired molecule. The third reaction is radical decomposition in a unimolecular reaction, forming a new radical and a spin‐paired...
2.1K
02:24Acid-Catalyzed Ring-Opening of Epoxides
7.4K
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...
7.4K