发现和描述具有独特生物合成特征和抗炎活性的菌兰西
Xiaotong Wang1,2, Xiaoyu Chen1,2, Zong-Jie Wang1,2
1State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, P. R. China.
Journal of the American Chemical Society
|July 19, 2023
概括
我们发现了myxococcin, 一种来自myxobacteria的新型兰氏, 通过aminopeptidase MfuP的处理产生抗炎化合物.
科学领域:
- 微生物学
- 生物化学
- 结构生物学
背景情况:
- 菌株基因组包含各种生物合成基因集群的二次代谢物,包括核糖体合成和翻译后修改的 (RiPP).
- 菌RiPPs的生物合成能力尚未得到充分研究,这代表了重要的知识差距.
研究的目的:
- 来识别和描述来自菌的新型RiPP.
- 阐明一个新发现的兰西,myxococcin的独特的生物合成途径和酶机制.
- 研究菌素的生物活性和结构特征.
主要方法:
- 基因组挖掘和生物信息分析以识别潜在的RiPP基因集群.
- 关键酶 (MfuM,MfuC,MfuP) 的生物化学表征,这些酶参与了myxococcin的生物合成.
- 对M61家族氨基酶MfuP的X射线结晶学和结构分析.
- 在体外测试以评估myxococcin的抗炎活性.
主要成果:
- 来自*Myxococcus fulvus*的新型兰西的鉴定和特征
- 一个级联生物合成途径的解,其中包括II类兰氏合成酶 (MfuM) 和I类兰氏环酶 (MfuC).
- 在RiPP生物合成中,MfuP是第一个描述的M61家族氨基酶,其表现为在转化甲菌素到甲菌素B中的内酶活性.
- 在没有细胞毒性的情况下,myxococcin在脂聚糖诱导的巨细胞中表现出抗炎作用.
结论:
- 可是一种具有独特生物合成机制的新型兰氏.
- M61家族氨基酶MfuP通过领导者独立的,结构选择性的胺键水解在RiPP成熟中起着至关重要的作用.
- 作为抗炎药物,myxococins具有潜在的治疗应用.
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