两株南海深海来源放线菌次级代谢产物研究

The deep-sea-derived actinomycetes have ability to adapt itself to the stress marine environment with new metabolic pathways and physiological functions different from terrestrial one, which in turn can produce novel compounds with more chemical diversities and bioactivities. There are numerous of actinomycetes have been discovered from the deep sea of the South China Sea, which indicate the abundant actinomycete resources. In this research, two deep-sea-derived actinomycetes Micromonospora sodiiphilus SCSIO 02972 and Streptomyces sp. SCSIO 11863 from the South China Sea with excellent antibacterial or cytotoxic activities will be chosen to study based on the screening of antibacterial activity, brine shrimp lethality and the chemical diversity. The approach to enhance the diversity of microbial natural products by alteration of easily accessible cultivation to active the presence of cryptic gene clusters will be optimized, and then the target strains will be fermented in a large scale after de-duplicate analyzing. The compounds will be isolated, whose structure will be elucidated by NMR, MS, IR, UV and X-ray, and their bioactivities will be estimated by antibacterial and cytotoxic experiment models. This research will explore a innovative way to enrich the new natural products database and to develop new drugs, which will also promote the utilizing of the marine resources and the expanding of the marine economy.

深海来源放线菌具有与陆生放线菌所不同的代谢多样性，能够产生结构新颖，活性独特的次级代谢产物。近年来，已经有大量来源于南海深海的放线菌被发现，说明南海深海具有丰富的放线菌资源。本项目在前期筛选的基础上，选择两株来源于南海深海，具有良好抗菌活性或卤虫致死活性的菌株Micromonospora sodiiphilus SCSIO 02972和Streptomyces sp. SCSIO 11863进行研究。本项目拟通过优化发酵条件来激活菌株中沉默基因的表达，使其能够产生多种结构类型的化合物；在化学排重的基础上，选择合适的培养条件进行放大发酵培养，通过代谢产物的提取分离，获得单体化合物；并通过核磁、质谱、红外，紫外及X-ray单晶衍射等方法解析其化学结构，通过抗菌和抗肿瘤实验模型评价其生物活性。以期为丰富新天然产物化合物库和新药的开发探索新的途径，也为开发利用海洋资源，发展海洋经济提供一定支持。

深海来源放线菌具有与陆生放线菌所不同的代谢多样性，能够产生结构新颖，活性独特的次级代谢产物。近年来，已经有大量来源于南海深海的放线菌被发现，说明南海深海具有丰富的放线菌资源。本项目优化了2株南海深海沉积物来源放线菌的发酵培养条件及次级代谢产物的提取方法，从中分离化合物30多个，鉴定结构的有15个，其中新结构化合物有6个。此外，还证明了黄素氧化酶XiaK能够催化海洋放线菌来源Xiamycin A中咔唑环上N的羟化形成N-hydroxyxiamycin，该化合物不稳定，能够进一步通过自由基中间体形成其他衍生物；通过操纵调控基因激活深海来源放线菌Streptomyces sp. SCSIO 02999中沉默TPMs生物合成基因簇的表达，分离得到11个TPMs衍生物，其中9个为新化合物，发表SCI论文4篇，申请专利2项。本项目的研究丰富了新天然产物化合物库，探索了新药开发的新途径，也为开发利用海洋资源，发展海洋经济提供一定支持。