一类新颖结构的链霉菌源Vicenistations类抗肿瘤成分研究

A wide range of important secondary metabolites, including antibiotics, herbicides, and growth promoting substances, are produced by several members of the actinomycetes. Streptomyces is the largest antibiotic producing genus among the actinomycetes; more than 60% of the nearly 6000 antibiotics of microbial origin.are produced by Streptomyces spp. including both antibacterials and antifungals and a considerable number of other bioactive compounds such as immunosuppressants and anticancer agents. Accordingly, Streptomyces strains, as prolific sources of a lager number and wider variety of new antibiotics, have been continuously noted rather than any other actinomycete genera. .During the course of our investigation on the bioactive components of microorganisms, a new 20-atom macrocyclic lactam metabolite named sannastatin and two anoluges were isolated and identified from a culture broth of S. sannanensis,.which was found in the feces of Ailuropoda melanoleuca.This is the first time that we discovered a vicenistatin analogues from this strain. Based on our previously research on vicenisations, we got another three Streptomyces strains which can produce vicenisations. Using three tumor cell as targets, Natural products chemistry and modern biofermentation theory as the basis, bioactivity-directed isolation was used to find vicenisations.we expected to find the ideal of the active ingredient or leading compounds from this strains. In addition, optimization of fermentation conditions could provide an effective way for the production of active compounds. The implementation of this project can be the foundation for further research on vicenistations drugs produced by Streptomyces, and also have important theoretical and practical significance of our own intellectual property of anticancer drugs.

放线菌是发现新颖活性天然产物重要来源，其中主要来源于链霉菌。Vicenistations是一类近年来从链霉菌里发现的具有显著抗肿瘤、抗菌活性的天然产物。.基于前期我们在vicenistations研究的基础上，我们又从大熊猫粪便里筛选到3株能产生vicenistations的链霉菌。以天然产物化学和现代生物发酵理论为基础，3株肿瘤细胞为靶标，在生物活性追踪指导下，对3 株链霉菌中新颖结构的vicenistations 类成份进行分离纯化，结构鉴定及抗肿瘤活性研究，有望从中筛选出理想的活性成分或先导化合物。除此之外，对产生目标化合物的菌株进行发酵条件优化，旨在为生产目标活性化合物提供有效途径。项目实施可为进一步为链霉菌来源的vicenistations类药物研究打下基础，对于创制出具有我国自主知识产权的抗肿瘤药物具有重要的理论价值和现实意义。

微生物已经成为寻找新颖结构活性天然产物的重要生物资源，在我们长期从微生物中寻找活性化合物的过程中，vicenistations引起了我们极大的兴趣。在前期的研究过程中，我们筛选到了三株菌，可以产生这类抗肿瘤活性成分。在国家自然科学基金的资助下，以天然产物化学的理论和现代发酵技术为基础，以海虾和一些重要的肿瘤细胞为靶标，采用生物活性追踪的分离技术从这些菌株分离活性成分，并采用现代波谱技术，如紫外光谱、红外光谱、质谱及核磁共振波谱技术鉴定了他们的化学结构。经过三年不懈的努力，具体研究结果如下：1. 分离到的2个为新结构的化合物，所有分离鉴定的这类化合物在活性测试中都显示出明显的活性。2. 研究结果发表多篇SCI论文，其他研究成果正在整理发表或申请专利当中。3. 培养了2名研究生和多名本科生。项目的实施的重要意义表现在多方面，例如它为将来进一步深入系统研究和开发新型抗肿瘤先导化合物提供方便，也为将来申请国家自然科学基金面上项目和其他项目鉴定基础。