三七活性成分诱导下的三七内生菌新颖活性代谢产物及其功能研究

Endophytes and their host plant have established a mutually beneficial relationship in the plant micro-ecosystems. Their primary and secondary metabolisms can be interacted and be influenced by each other, leading to the synthesis of novel metabolites in host and endophytes. Sanqi (Panax notoginseng) is a particular and valued Chinese medicine in China. It’s crude material and preparations have been widely used in clinical. Studies presented that Sanqi possessed a broad spectrum of biological and pharmacological properties derived from its active ingredients. A variety of endophytes are harbored in Panax notoginseng, but little is known about the effects of the active ingredients of host plant to them. As the data present that endophytes can serve as a reservoir of active natural product, whether the active molecules of Panax notoginseng induce the secondary metabolism of the endophytes to produce novel metabolites with some activities? Herein, in this proposal, we plan to investigate the potential of producing novel secondary metabolites of Panax notoginseng endophytes with the induction of the active ingredients derived from Panax notoginseng. The effector and the metabolism pathway will be analyzed, and bioactivities also be screened with antitumor, lipid-lowering, antimicrobial models. Our aims are to: (1) find novel molecules from Panax notoginseng endophytes with the induction of the active components of their host plant; (2) investigate the metabolic mechanisms and pathways involved in the induced producing novel products of endophytes; (3) explore the potent bioactivies of the novel entities.

植物内生菌与宿主植物形成了一种互利互惠的共生关系，在初级代谢和次级代谢中具有互相作用，可以诱导植物和内生菌产生新的代谢产物。植物内生菌能够产生大量的生理活性物质。三七是我国特有的名贵中药，药材和制剂广泛应用于临床治疗中；其活性成分众多，药理作用广泛。但三七这些活性成分对生活在其植物体体内的丰富内生菌作用如何，能否诱导内生菌的代谢途径及新颖代谢产物的生成及其代谢产物的活性尚未有研究。本项目拟以三七活性成分为诱导因子，模拟内生菌的生存环境，探索三七内生菌产生新颖结构的代谢产物能力，分析代谢产物生成的影响因子及途径，并以抗肿瘤、降脂、抗菌等活性模型进行活性筛选。项目研究目的：探索三七活性成分诱导下的三七内生菌产生的新颖活性代谢产物及其功能，为开发微生物药物提供物质基础和理论基础。

宿主植物成分对其内生的微生物生长与代谢均具有影响作用。在本项目经费的支持下，我们以三七提取物或三七总皂苷为添加物，开展其诱导三七内生菌（真菌、细菌）的代谢产物与代谢生长的影响作用，获得其活性代谢新产物并探索其功能与活性，为进一步挖掘三七内生菌的资源与用途提供基础。.虽然受到2年之久的新冠疫情的影响，在团队师生共同努力下，从三七中分离得到89株内生真菌和143株内生细菌，并以三七提取物和三七总皂苷为添加物，筛选出18株代谢产物变化较大的内生菌菌株。对这18株菌株以ITS-4、ITS-4（真菌）和16S rRNA基因序列进行了分类鉴定，初步确定了其分类地位。从其中的10株内生菌的代谢产物中分离鉴定了192个化合物，其中新化合物23个。发现一些菌株在添加三七活性成分时，可刺激其快速生长，并可转化为病原微生物，产生可影响三七叶纤维素和生化酶的活性而致三七病害；发现了一些具有抗菌和抗耐（多）药菌的新化合物，报道了一个已知化合物的抗菌活性及其破坏细菌细胞膜、清除耐药菌生物膜的功能。筛选到的其他菌株的代谢产物以及其生物活性与功能的研究工作还在深入进行中。.到2021年底，团队依托该项目共发表SCI收录的科研论文4篇、获得授权的中国发明专利3项。项目负责人成功晋升为正高职称；培养毕业硕士生7名，本科毕业生5名；在读研究生12名。