结合剂是内生菌Trichocladium sp sp的结合剂衍生物
Viktor E Simons1, Attila Mándi2, Marian Frank1
1Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Pharmaceutical Biology and Biotechnology, Universitätsstrasse 1, Düsseldorf 40225, Germany.
Fitoterapia
|March 20, 2024
概括
通过OSMAC的方法,增强了Trichocladium sp.中的代谢物产量,产生了五种新的化合物. 一种新化合物显示出强大的抗菌和细胞毒性作用.
科学领域:
- 微生物学 微生物学
- 自然产品化学 自然产品化学
- 菌生物技术是一种真菌生物技术.
背景情况:
- 通过OSMAC (one strain many compounds) 概念,在各种条件下培养微生物,以增加二次代谢物多样性.
- 内生菌是新型生物活性化合物的丰富来源.
- 特里科克拉 sp. 的存在. 是一种内性真菌,具有产生独特代谢物的潜力.
研究的目的:
- 研究氨补充剂对Trichocladium sp.中二次代谢物产生的影响. 使用OSMAC的方法.
- 发现和阐明来自Trichocladium sp.的新化合物的结构.
- 评估分离化合物的生物活性.
主要方法:
- 通过补充Trichocladium sp.的培养基来应用OSMAC方法. 含有2.5%的 fenilalanine. 这是一个很好的方法.
- 使用色谱技术分离和净化二次代谢产物.
- 通过全面的光谱测量 (NMR,MS) 和TDDFT-ECD计算来阐明新化合物的结构,以获得绝对配置.
- 对抗黄金葡萄球菌和结核菌菌的抗菌活性的评估.
- 对人类单细胞细胞系THP1.1的细胞毒性影响的评估.
主要成果:
- 分离了五种新的化合物 (三甲基醇,三甲基酸,甲酸,甲酸,甲酸) 和五种已知的化合物.
- 新化合物的结构得到了阐明.
- 为化合物3-5提出了一个生物合成途径.
- 化合物6表现出强烈的抗菌活性对抗耐甲基金色葡萄球菌 (MIC = 0.78μM) 和显著的细胞毒性对THP1细胞 (IC50 = 0.7μM).
- 化合物8对Mycobacterium结核病 (MIC = 25 μM) 具有中度的抗菌活性,对THP1细胞具有较弱的细胞毒性 (IC50 = 42 μM).
结论:
- OSMAC方法,特别是氨补充剂,在诱导Trichocladium sp.新型二次代谢物的产生方面是有效的.
- 隔离的化合物,特别是化合物6,具有显著的抗菌和细胞毒性,突出显示了它们作为治疗的潜力.
- 需要对这些化合物的生物合成途径和药理活动进行进一步的研究.
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