黄翅大白蚁抗菌活性放线菌发掘与抗真菌化合物鉴定

放线菌是抗菌药物的重要来源，随着耐药菌和新型致病菌的不断出现，有必要从新的生境中寻找新的放线菌资源和活性化合物。培菌白蚁是体内与细菌、古菌和真菌等多种微生物共生、体外菌圃(蚁巢)与特定真菌共生的一类白蚁，其独特的生活习性和生存环境可能孕育出具有独特次级代谢产物的微生物，其共生菌是发掘新型微生物药物的重要资源。本项目以培菌白蚁黄翅大白蚁为材料，通过肠道和菌圃微生物多样性分析，放线菌分离鉴定及抑菌活性筛选，发掘具有抗菌活性的放线菌和活性化合物；重点对该白蚁前肠中分离的两株放线菌进行抗真菌活性成分追踪纯化，解析其化合物结构；根据基因组序列信息，预测其合成基因簇，进一步通过基因敲除和表达分析，确定活性化合物的生物合成基因簇，并通过大片段直接克隆实现基因簇的异源表达和产物大量生产。通过本研究，预期将积累丰富而独特的菌株和基因资源，获得新的具有抑菌活性的化合物，为进一步药物开发提供先导化合物资源。

Actinomycetes are an important source of antimicrobial drugs. With the emergence of resistant bacteria and pathogens, it is necessary to find new actinomycetes resources and active compounds from new habitats. Fungus-growing termites have symbiosis with many kinds of microbes including bacteria, archaea and fungi in vivo and with specific fungi in their nest. Their unique living habits and living environments may foster various kinds of microbes with unique metabolic mechanisms, which may provide important resources for discovering new antimicrobial drugs. In this study, fungus-growing termite Macrotermes barneyi will be used as experimental material. Through analysis of the microbial diversity of the intestinal tract and the nest, isolation and identification of actinomycetes as well as detection of antimicrobial activity, the actinomycetes with antimicrobial activity will be discovered. Studies on two strains of actinomycetes isolated from the foregut will be focused. The antifungal active components will be traced and purified, and the structures of the compounds will be analyzed. Based on genomic sequence information, the corresponding gene clusters will be predicted. Further the gene clusters of active compounds will be determined by gene knockout and expression analysis. Heterologous expression and high yield production will be achieved through the Large Fragment Direct Cloning technology. It is expected that rich and unique strains and genetic resources will be accumulated, and novel compounds with antimicrobial activity will be obtained. These will further provide novel lead compound resources for drug development.