基因组挖掘导致来自北极衍生的真菌的各种具有抗炎活性的基
Yaodong Ning1, Qinwufeng Gu2, Te Zheng3
1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, People's Republic of China.
Journal of natural products
|May 1, 2024
概括
在Eutypella sp.中删除一个关键基因. D-1激活了休眠基因,产生了新的生物活性化合物. 发现了8种新的甲,其中一些显示出显著的抗炎作用和调节关键信号通路.
科学领域:
- 微生物学和自然产品发现
- 生物信息学和代谢工程
- 药理学和药物发现
背景情况:
- 生物信息学和分离技术的进步有助于发现新的生物活性化合物.
- 代谢工程策略,如基因删除,可以诱导产生以前未经表征的二次代谢产物.
- 这种真菌是Eutypella sp. D-1 是各种化学实体的潜在来源.
研究的目的:
- 研究删除三烯环酶生物合成基因对Eutypella sp.中二次代谢产物的影响. D-1.1.1 在这个问题上.
- 隔离,阐明结构,并评估由工程菌株产生的新型化合物的生物活性.
- 为了推断代谢转途径,负责改变代谢物概况.
主要方法:
- 在Eutypella sp.中进行基因挖掘和向基因删除. D-1.1.1 在这个问题上.
- 复合物分离的先进分离技术 (例如色谱) 用于化合物分离.
- 光谱方法 (HRESIMS,NMR) 和ECD计算用于结构阐明.
- 在体外测试 (氧化释放,细胞毒性) 和体内模型 (斑马鱼) 用于生物活性评估.
主要成果:
- 关键基因的删除导致了代谢转换和15种基的产生,其中包括8种新化合物.
- 鉴定了六种不同的基骨类型,其中一种具有新的5/10宏环乙烯结构.
- 化合物6,8,11,14和15表现出抗炎活性,没有细胞毒性.
- 阿科兰类型的8抑制了氧化的产生,调节了MAPK和NLRP3/caspase-1通路,减少了斑马鱼的神经炎症.
结论:
- 有针对性的基因删除是揭示神秘生物合成途径和发现新型天然产品的有效策略.
- 已识别的甲,特别是第8化合物,为抗炎药物开发提供了有前途的线索.
- 这项研究提供了对代谢变流及其在二次代谢物多样化中的作用的见解.
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