リボソームで合成されたチオペプチド抗生物質は,延長因子Tuを標的とする
Rowan P Morris1, Jennifer A Leeds, Hans Ulrich Naegeli
1Natural Products Unit, Novartis Institutes for BioMedical Research, Basel, 4056, Switzerland.
Journal of the American Chemical Society
|April 3, 2009
まとめ
新しいチオペプチド抗生物質であるチオムラシンが,珍しい細菌から発見されました. バクテリアの延長因子Tu (EF-Tu) を標的にし,低抵抗力を持つ黄色のステーキ菌に対する新しい戦略を提供します.
科学分野:
- 微生物学 微生物学とは
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- ティオペプチド (Thiopeptides) は,中央ヘテロサイクルのリングシステムを持つマクロサイクルの高度に改変されたペプチドのクラスです.
- チオペプチド抗生物質はリボソームで合成され,染色体でコードされます.
- 多くのチオペプチドの生合成経路は,未だに曖昧である.
研究 の 目的:
- Staphylococcus aureusを標的とした新種の抗生物質を特定する.
- 新しいチオペプチドファミリーであるチオムラシンの生物合成経路を解明する.
- ティオムラシンの分子標的と耐性プロフィールを決定する.
主な方法:
- 希少なアクチノミセト菌の抗菌活動に対する抗菌性のスクリーニング Staphylococcus aureus.
- チオペプチド遺伝子クラスタを特定するためのゲノムマイニング.
- バイオケミカルアッセイは,チオムラシンの標的を決定する.
- バクテリア耐性選択試験.
主要な成果:
- ノノムラエア種からの新しいチオペプチドファミリーであるチオムラシンの識別.
- チオムラシンおよび関連チオペプチドの生物合成経路の解明.
- ティオムラシンが細菌の延長因子Tu (EF-Tu) を標的にすることを決定.
- ティオムラシンは,レジスタンスの発生傾向が低く,既存の抗生物質とのクロスレジスタンスはなく,Staphylococcus aureusに対して強力な活性を示します.
結論:
- ティオムラシンは,未開発の細菌機構を標的とした有望な新種の抗生物質です.
- この発見は,チオペプチド生物合成の洞察と,新しい抗生物質の設計の可能性を提供します.
- ティオムラシンは,抗生物質耐性細菌感染症と戦うための潜在的な解決策を提供します.
関連する概念動画
Inhibitors of Bacterial Protein Synthesis
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Types of RNA
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Riboswitches
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
Transcription Attenuation in Prokaryotes
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...


