中文摘要
Streptomyces sp. SCSIO 03032是从深海沉积物中分离得到的链霉菌属新种,基因组测序结果表明它含有编码多种类型次级代谢产物的生物合成基因簇。前期研究中,我们从中分离到结构新颖的双吲哚螺环生物碱spiroindimicins A-D及大环内酰胺heronamides D-F。鉴于Streptomyces sp. SCSIO 03032蕴藏着巨大的次级代谢产物合成能力,本项目拟以生物信息学分析为指导,采用OSMAC、同位素示踪、异源表达、调控基因调节、功能基因敲除等生物学手段,结合HPLC-DAD-UV、LC-MS的化学分析、排重方法,对该菌株的次级代谢产物进行深度挖掘,以期获得结构新颖的天然产物,为微生物药物提供先导化合物。同时,结构新颖的化合物蕴藏着新颖的酶学机制,本项目也为研究新的酶学机制提供基础,为合成新的小分子化合物提供灵感。
英文摘要
In the past decade, marine actinomycetes have been documented as a significant resource for producing novel secondary metabotites of leads for drug discovery, as many novel metabotites with anti-infective and antitumor activities have been identified from such organisms. Particularly, many of these were obtained from new genera or species of marine actinomycetes. The strain Streptomyces sp. SCSIO 03032 was isolated from a sediment sample (E 87 59.70, N 9 59.30) at a depth of 3412 m from the Bay of Bengal in the Indian Ocean and it was identified as a new species on the basis of its 16S rRNA gene sequence. Four new bisindole alkaloids spiroindimicins A-D and three polyketide macrolactams heronamides D-F were obtained from the fermentation broth of Streptomyces sp. SCSIO 03032 in our previous work. Further to evaluate the biosynthetic potential of this strain, the whole genome (6,243,587-bp) of SCSIO 03032 has been sequenced and all identifiable secondary metabolism gene clusters were analyzed. Genome analysis revealed 26 secondary metabolic biosynthesis gene clusters in complete genome sequence. Based on these data, we intend to use the method of genome mining to discover new natural products from the strain SCSIO 03032. Genome sequencing based mining as new strategies are powerful model can be employed for discovering new natural products. Numberours of novel natural products were discovered from sequenced microbes by genomics-guided approaches. In this current project, we intend to use one strain many compounds method (OSMAC), feeding with isotope-labelled precursors, heterologous expression, activation of silent gene clusters, and functional gene knockout, coupled with the analysis methods of HPLC-DAD-UV、LC-MS to discover new secondary metabolites from the strain Streptomyces sp. SCSIO 03032. Natural products and their derivatives form the basis of many important drugs that have found wide spread use in the clinic and new secondary metabolites obtained from SCSIO 03032 may form the basis for new drug leads. Besides, the structure of the novel compound bears a novel enzymatic mechanism. The project also provides a new basis for microbiologists to study the enzymatic mechanism, and provide inspiration of organic synthesis of small molecular compounds for organic chemists.
