由非核糖体合成酶基因集群启发的抗菌药物
Xavier Vila-Farres1,2, John Chu1,2, Daigo Inoyama1,2
1Laboratory of Genetically Encoded Small Molecules and ‡Proteomics Resource Center, The Rockefeller University , New York, New York 10065, United States.
Journal of the American Chemical Society
|January 6, 2017
概括
研究人员绕过了细菌培养,发现了新的治疗方法. 生物信息预测和化学合成产生了合成生物信息天然产品 (syn-BNPs),包括一种强大的抗生素和抗真菌剂.
科学领域:
- 微生物学
- 合成化学
- 生物信息学
背景情况:
- 细菌培养提取物是治疗开发的传统来源.
- 培养方法限制了细菌生物合成多样性的全部范围.
- 由于培养的局限性,很大一部分潜在的微生物疗法仍未被发现.
研究的目的:
- 开发一种绕过细菌培养的新药发现方法.
- 通过生物信息学预测和化学合成细菌基因集群中的新型小分子.
- 从这种新型化合物中确定新的抗菌和抗真菌剂.
主要方法:
- 来自生物合成基因序的小分子结构的生物信息预测.
- 预测结构的化学合成以创建合成生物信息自然产品 (syn-BNPs).
- 针对微生物病原体的非核糖体合成酶启发的syn-BNPs的查.
主要成果:
- 发现了一种新型抗生素, 没有可识别的抗药机制.
- 对一系列真菌病原体有效的抗真菌剂的鉴定.
- 证明syn-BNP方法在发现新疗法的有效性.
结论:
- 生物信息预测和合成策略显著扩大了对细菌生物合成多样性的获取.
- 这种方法为发现新型抗生素和抗真菌药物提供了强大的平台.
- 鉴定到的syn-BNPs为新的抗感染疗法提供了有希望的线索.
相关概念视频
Gene Regulation in Microbial Communities: Quorum Sensing
800
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
800
Antimicrobial Proteins
14.9K
Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
14.9K
Types of RNA
73.5K
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...
73.5K
Development of Antibiotic Resistance
1.7K
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
1.7K
Antibiotic Selection
61.7K
Overview
61.7K
Peptidoglycan Synthesis
3.6K
Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan...
3.6K


