一个双功能甲基转移酶在抗瘤抗生素斯特雷普托尼格林的生物合成中
Xiaozheng Wang1, Xinyue Xie1, Jing Wo1,2
1State Key Laboratory of Microbial Metabolism, Joint International Laboratory of Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China.
Chembiochem : a European journal of chemical biology
|July 6, 2024
概括
研究人员对O-甲基转移酶StnQ2进行了表征,揭示了它在斯特列尼格林生物合成过程中甲基化基和基基中的双重作用. 这有助于我们更好地理解甲基转移酶和完整的链条尼格林通路.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 斯特列尼格林 (STN) 是一种氨基类类抗生素,以其强烈的抗瘤活性而闻名.
- STN具有复杂的结构,有四个甲基,包括C-甲基和O-甲基类型.
研究的目的:
- 在生物化学上表征O-甲基转移酶StnQ2参与链蛋白生物合成.
- 阐明StnQ2在基和基组上的特定甲基化活性.
主要方法:
- 对 StnQ2.2 的酶净化和活性试验.
- 对StnQ2的基质特异性和催化机制的生物化学表征.
主要成果:
- 确定StnQ2是一种O-甲基转移酶,可催化氧基和氧基的甲基化.
- 这种双甲基化活性对于链红素的生物合成至关重要.
- 这些发现为甲基转移酶的功能多样性提供了新的见解.
结论:
- 对StnQ2的表征提供了关键步骤,以了解链蛋白的完整生物合成途径.
- 这项研究增强了对甲基转移酶及其在天然产品合成中的作用的了解.
- 这些发现有助于更广泛的抗生素和抗瘤化合物生物合成领域.
更多相关视频
相关概念视频
Phase II Reactions: Methylation Reactions
174
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
174
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Transcription Attenuation in Prokaryotes
15.2K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.2K
Phase II Reactions: Acetylation Reactions
213
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
213
Phase II Reactions: Miscellaneous Conjugation Reactions
58
Phase II biotransformations are detoxification mechanisms that conjugate xenobiotics with endogenous substances, neutralizing their toxicity.
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
58


