项目名称： 三株拟茎点霉菌次生代谢产物及其抗耐甲氧西林金黄色葡萄球菌活性研究

项目编号： No.21462051

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 杨海英

作者单位： 云南民族大学

项目金额： 50万元

中文摘要： 我国是滥用抗生素最严重的国家，为了应对日益严重的MRSA感染，寻找对耐药细菌有显著活性的新骨架抗菌素非常迫切。项目前期发现滇重楼内生拟茎点霉菌代谢产物非常丰富，仅对1株菌的初步研究就得到19个新化合物(包括4个类型的新骨架)，部分化合物抗MRSA活性显著。鉴于上述新发现，项目组继续对源于滇重楼的25株拟茎点霉菌进行小样发酵，通过HPLC分析和粗提物活性筛选，精选出3株次生代谢产物丰富、差异明显、活性相对突出的菌株。项目将对这3株菌株进行放大发酵，对其活性部位的化学成分进行深入研究。预期将从三株菌发酵产物中分离到次生代谢产物100个以上(新化合物超过30个)，力争发现3-5个新骨架化合物或筛选到3-5个抗MRSA活性突出的化合物，为抗MRSA药物开发提供先导性化合物。对有前景的活性化合物，项目组将以化合物为指标进行发酵条件优化。此外，还将选对部分活性好的化合物的抗菌机理和构效关系进行研究。

中文关键词： 拟茎点霉菌；次生代谢产物；耐甲氧西林金黄色葡萄球菌；活性

英文摘要： China is one of the countries most affected by the abuse of antibiotics in the world, and it is urgent to develop effective new strategy and drugs with new mechanism to control MRSA infections. However, the discovery of new skeleton antibiotics is prerequisite for sustainable fight against drug-resistant bacterial. In our search for metabolites from a stain of Phomopsis sp. isolated from the rootstock of Paris polyphylla Smith var. yunnanesis, 19 novel compouds with antibacterial activity had been isolated including four new skeleton compounds. All of novel compounds were screened for their anti-MRSA activity, and some of them showed significant activity. In the light of the findings of the studies , 25 strians of the genera Phomopsis from the rootstock of Paris polyphylla Smith var. yunnanesis were studied by our team. Three strains of them were selected based on the diversity of secondary metabolites, the differences of secondary metabolites among strains and the anti-MRSA activity of the extracts from the strains by HPLC spectra analysis and anti-MRSA activity evaluation. The fermentation scale-up of those strains will be carried out, and the chemical constituents of active fraction will be studied intensively in this project. At least 100 secondary metabolites including 30 novel compounds could be separated from fermentation products of the strains in the project. We will try to find 3-5 compounds of outstanding activity against MRSA. These compounds could be considered as leads, which become candidates for anti-MRSA drug development.Optimization of fermentation conditions will be operated based on the yield of those promising compounds. In addition, the antibacterial mechanism and structure-activity relationship of some compounds with great activity will be studied in this project.

英文关键词： Phomopsis;secondary metabolites;MRSA;activity