动物编码的非核糖体通道到布尔萨特林类似物
Aarthi Venugopalan1, Eric W Schmidt1
1Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
Journal of the American Chemical Society
|February 11, 2025
概括
海洋软体通过一种新的动物生物合成途径产生有毒的bursatellin-oxazinin化合物. 这一发现揭示了
科学领域:
- 海洋天然产品化学
- 动物生物化学和基因组学
- 自然产品的生物合成
背景情况:
- 布尔萨特林-奥克萨辛化合物是氨酸衍生的海洋天然产品,存在于软体动物中.
- 这些化合物已与毒性有关40年, 但它们的来源仍然未知.
- 之前的研究缺乏对软体生物合成途径的了解.
研究的目的:
- 为了确定软体动物中的bursatellin类代谢物的生物合成来源.
- 在生物化学上描述参与布尔萨特林生物合成途径的基因.
- 研究这些化合物在软体动物中的进化和生态意义.
主要方法:
- 软体动物基因组和转录组的生物信息分析以确定基因集群.
- 确定路径 (bur-ox) 中关键酶的生物化学特征.
- 酶测试以阐明代谢物合成中的减少和修改步骤.
主要成果:
- 在软体动物中发现了一种新的bursatellin生物合成基因集群 (bur-ox通路).
- 生物化学证据表明是软体而不是微生物共生体产生这些化合物.
- 在关键合成步骤中参与的非核糖体合成酶 (NRPS) 和氨基碳酸转移酶 (ACT) 的表征.
结论:
- 软体动物具有独特的动物衍生的NRPS途径,用于合成布尔萨特林类化合物.
- 这些代谢物的广泛分布表明这些代谢物的共同起源和生理作用.
- 存在于可食用的双动物中,引发了有关素毒性的疑问,并突出了动物的化学多样性.
更多相关视频
09:08From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
17.1K
07:59A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
9.7K
相关概念视频
Biosynthesis in Bacteria
1.0K
Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
1.0K
Amino Acid Biosynthetic Pathways
1.8K
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...
1.8K
Production of Pharmaceuticals
100
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under...
100
Regulation of Bacterial Virulence
81
Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
81
Inhibitors of Gram-positive Cell Wall Synthesis
225
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...
225
Inhibitors of Bacterial Protein Synthesis
127
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...
127
