ペプチド天然産物生物合成におけるアスパート酸をアミノマロナ酸に変換する2段階の酵素カスケードの発見
Hye Won Kim1, Sangwook Kang2, Sihyeon Kim1
1Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Journal of the American Chemical Society
|June 5, 2025
まとめ
アミノマロン酸 (Ama) 生合成のための新しい2酵素経路が発見されました. この経路は,SmaOとSmaX酵素を用いてアスパルテートをAmaに変換し,天然製品生物合成で広く使用されています.
科学分野:
- 生物化学
- 自然製品の生物合成
- 酵素学
背景:
- アミノマロン酸 (Ama) は天然製品の成分ですが,その生物合成経路は十分に理解されていません.
- リボソーム合成および翻訳後の改変ペプチド (RiPP) は新しい酵素化学の源となる.
研究 の 目的:
- アミノマロン酸 (Ama) の生物合成経路を解明する.
- Amaの生成に 責任のある酵素を特定する
- この経路の分布を自然産物生物合成で調べる
主な方法:
- RiPP生物合成遺伝子クラスタの利用
- 2つの新しい酵素の識別と特徴付け:SmaO (Fe (II) /2-オキシグルタレート依存酸素酶) とSmaX (非典型のFe (II) 依存ヒスティジンアスパルテートドメイン酵素).
- 関連する生物合成経路のバイオ情報分析
主要な成果:
- アスパルタ酸からアマ生物合成のための新しい2酵素経路が特定され,β-ヒドロキシアスパル酸の中間体を経由した.
- SmaOはアスパルタ酸を水酸化し,SmaXはα-ヒドロキシ酸中間体で4電子の酸化C-C結合分裂を行う.
- SmaXは,他の知られているHDドメイン酸素酶とは異なる,単一のFe共因子をC-C結合分裂に使用します.
結論:
- アミノマロン酸の新生合成経路が発見されました.
- SmaOとSmaXを含む2つの酵素のカスケードは,RiPPと非リボソームペプチド (NRP) を含む様々なペプチド天然産物の生物合成に広く使用されている可能性が高い.
さらに関連する動画
09:14Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
12.2K
14:42Liquid Chromatography Coupled to Refractive Index or Mass Spectrometric Detection for Metabolite Profiling in Lysate-based Cell-free Systems
Published on: September 23, 2021
5.1K
関連する概念動画
Amino Acid Biosynthetic Pathways
165
Amino acid biosynthesis is essential for cell growth, protein synthesis, and metabolic regulation. Cells generate essential and non-essential amino acids from metabolic intermediates to sustain vital biological functions. These intermediates originate from key metabolic pathways: glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Important precursors include α-ketoglutarate, pyruvate, oxaloacetate, phosphoenolpyruvate, and erythrose-4-phosphate, which...
165
Allosteric Proteins-ATCase
5.9K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.9K
Amino Acid Catabolism
213
Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
213
Biosynthesis of Nucleic Acids
207
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
207
Acid Halides to Amides: Aminolysis
3.1K
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
3.1K
Peptide Identification Using Tandem Mass Spectrometry
6.8K
Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
6.8K
