アリファティック・エーテル・ボンド形成は,天然製品生物合成におけるラジカルSAM酵素の範囲を拡大する
Kenzie A Clark1, Leah B Bushin1, Mohammad R Seyedsayamdost1,2
1Department of Chemistry , Princeton University , Princeton , New Jersey 08544 , United States.
Journal of the American Chemical Society
|June 28, 2019
まとめ
研究者らは,リボソーム合成および翻訳後の改変ペプチド (RiPP) で初めてエーテルクロスリンクを生成する新しい酵素を発見した. この発見により 微生物の天然産物生物合成と 酵素触媒の理解が広がりました
科学分野:
- 生物化学
- 分子生物学
- バイオ情報学
背景:
- 微生物の天然製品は新しい酵素変換の貴重な源である.
- リボソームで合成されたペプチドと翻訳後のペプチド (RiPP) は,多様な自然産物である.
- ラジカルS-アデノシルメチオニン (RaS) 酵素は独特の生化学反応を触媒化する.
研究 の 目的:
- 新しい生物情報検索戦略によって特定された新しいRaS酵素を特徴づける.
- RiPP遺伝子クラスター内のRaS酵素の触媒的活性を調べる
- 新しい RiPP 改変経路とヘテロサイクリング モチーフを探求する.
主な方法:
- RaS金属酵素を含むRiPP遺伝子クラスタを特定するためのバイオ情報分析.
- 特定のRaS酵素の生化学的特徴
- 結果の翻訳後の修正とヘテロサイクリングの分析.
主要な成果:
- クオラムセンシングで調節されるRaS酵素による多数のRiPP遺伝子クラスタの識別.
- ThrとGlnの残留物間のアリファティックエーテルクロスリンクを形成するRaS酵素の特徴.
- これは,新しいヘテロサイクリングモチーフを形成する,RaS酵素によって触媒化されたエーテルクロスリンクの最初の例を表しています.
結論:
- この研究は,RiPPのバイオシンセシスにおける新しいRaS酵素触媒エーテルクロスリンク反応を明らかにした.
- この発見は,天然製品における 酵素的変化の既知のレパートリーを拡張します.
- バイオインフォマティクスのアプローチは,新しい RiPP 改変ファミリーの発見に有効です.
関連する概念動画
Enzymes
93.9K
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...
93.9K
Radical Formation: Overview
2.6K
A bond can be broken either by heterolytic bond cleavage to form ions or homolytic bond cleavage to yield radicals. A fishhook arrow is used to represent the motion of a single electron in homolytic bond cleavage. There are two main sources from which radicals can be formed:
Radicals from spin-paired molecules:
Radicals can be obtained from spin-paired molecules either by homolysis or electron transfer. While two radicals are formed in the former, an electron is added in the...
Radicals from spin-paired molecules:
Radicals can be obtained from spin-paired molecules either by homolysis or electron transfer. While two radicals are formed in the former, an electron is added in the...
2.6K
Radical Formation: Homolysis
4.3K
A bond is formed between two atoms by sharing two electrons. When this bond is broken by supplying sufficient energy, either two electrons can be taken up by one atom forming ions by the cleavage called heterolysis, or the two electrons are shared by two atoms, with one each creating radicals by the cleavage called homolysis.
4.3K
Radical Formation: Addition
2.2K
Radicals can be formed by adding a radical to a spin-paired molecule. This is typically observed with unsaturated species, where the addition of a radical across the π bond leads to the production of a new radical by dissolving the π bond. For example, the addition of a Br radical to an alkene yields a carbon-centered radical.
Similar to charge conservation in chemical reactions, spin conservation is implicit for radical reactions. Accordingly, the product formed must possess an...
Similar to charge conservation in chemical reactions, spin conservation is implicit for radical reactions. Accordingly, the product formed must possess an...
2.2K
Radical Formation: Abstraction
4.3K
The electron of an atom can be abstracted from a compound by a relatively unstable radical to generate a new radical of relatively greater stability. For example, an initiator which forms radicals by homolysis can abstract a suitable species like a hydrogen atom or a halogen atom from a compound to generate a new radical. This ability of radicals to propagate by abstraction is a crucial feature of radical chain reactions.
Even though homolysis produces radicals, it is different from radical...
Even though homolysis produces radicals, it is different from radical...
4.3K
Radical Formation: Elimination
2.2K
Another method of radical formation is the elimination process. It is the opposite of the addition route and is driven by the instability of the radical. For example, as depicted in Figure 1, dibenzoyl peroxide yields a pair of unstable radicals upon homolysis. Given its instability, this radical spontaneously undergoes elimination via a C–C bond cleavage to form a relatively more stable phenyl radical. The mechanism involves cleavage of the bond between the α and β positions with respect...
2.2K


