表观遗传修饰挖掘深海冷泉真菌CS-113和CS-164次级代谢产物化学多样性及抗人类致病细菌活性研究

批准号:
82003648
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
杨遂群
依托单位:
学科分类:
海洋药物
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
杨遂群
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中文摘要
人类致病细菌耐药性的出现与扩散对人类健康产生了巨大威胁,迫切需要新型、安全、高效抗生素的研发。海洋来源真菌是发现结构新颖、生物活性显著天然产物的重要来源。深海冷泉来源真菌的遗传背景和代谢途径更为复杂多样,且鲜有文献报道,更容易产生具有特殊化学结构和特殊生理活性和功能的物质,在抗耐药菌先导化合物研发方面具有巨大潜力。前期研究我们发现深海冷泉真菌CS-113和CS-164的代谢产物有着极大的化学多样性,并且对耐甲氧西林金黄色葡萄球菌等人类致病细菌具有显著抑制活性。而且发现,添加诱导剂能显著影响以上两株真菌的代谢产物类型。本项目拟在前期工作基础上,通过表观遗传修饰挖掘以上两株冷泉真菌的沉默代谢途径,以抗人类致病细菌活性为导向,以期发现具有新颖结构类型和良好抗菌活性的新型抗生素先导化合物,初步探讨其构效关系及抑菌作用机制并对其生物合成调控进行初步研究,为深海冷泉来源真菌的有效开发利用提供科学依据。
英文摘要
The emergence and wide spread of drug-resistant pathogenic bacteria pose a great threat to human health, urging to discover new types of antibiotics with high efficiency and safety. Marine derived filamentous fungi are rich sources of natural products possessing diverse scaffolds and bioactivities. The genetic background and metabolic pathway of deep-sea cold seep derived fungi are much more complex and diverse. As no report of deep-sea cold seep derived fungi has been published so far, it is more likely to produce substances with special chemical structure and special physiological activity, which have great potential in the research and development of lead compounds against drug-resistant bacteria. Our previous study showed that the metabolites of deep-sea cold seep derived fungi CS-113 and CS-164 have great chemical diversity and potent inhibitory activities against MRSA and some other human pathogenic bacteria. It was also found that the metabolism of the above two fungal strains could be significantly affected by the addition of inducers. On the basis of previous studies, guided by the activity of anti-human pathogenic bacteria, this project will focus on excavating the cryptic metabolism pathway of the above two deep-sea cold seep derived fungi by epigenetic manipulation, increasing the rate of secondary metabolites with diverse structures and potent activity against human pathogenic bacteria under optimized conditions and inducers, discussing their structure-activity relationship and antibacterial mechanism, carrying out preliminary study on the regulation of its biosynthesis, and providing scientific basis for the effective development and utilization of deep-sea cold seep derived fungi.
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DOI:10.1039/d3ob00058c
发表时间:2023
期刊:Organic & Biomolecular Chemistry
影响因子:--
作者:Sui-Qun Yang;Qi Song;Xiao-Ming Li;Xin Li;Hong-Lei Li;Ling-Hong Meng;Bin-Gui Wang
通讯作者:Bin-Gui Wang
DOI:10.1016/j.dsr.2023.104114
发表时间:2023-07-25
期刊:DEEP-SEA RESEARCH PART I-OCEANOGRAPHIC RESEARCH PAPERS
影响因子:2.4
作者:Chen, Xiao-Dan;Yang, Sui-Qun;Li, Xin
通讯作者:Li, Xin
DOI:10.3390/md20080529
发表时间:2022-08-18
期刊:Marine drugs
影响因子:5.4
作者:
通讯作者:
国内基金
海外基金
