海洋放线菌Streptomyces costaricanus SCSIO ZS0073中fungichromin生物合成基因簇的分析鉴定  

Identification of the fungichromin biosynthetic pathway from Streptomyces costaricanus SCSIO ZS0073

作　　者：贾艳玺 谢运昌[1] 李青连[1] 马俊英[1] 黄洪波[1] 鞠建华[1,2] 

机构地区：[1]中国科学院南海海洋研究所,中国科学院热带海洋生物资源与生态重点实验室,广东省海洋药物重点实验室,中国科学院海洋微生物研究中心,广东广州510301 [2]中国科学院大学,北京100049

出　　处：《中国海洋药物》2017年第6期1-10,共10页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金广东联合基金重点项目(U1501223);广东省自然科学基金团队项目(2016A030312014)资助

摘　　要：目的对分离自中国广西红沙红树林湿地公园的放线菌菌株Streptomycescostaricanus SCSIO ZS0073进行基因组测序分析,并对其生产的制霉色基素(fungichromin)的生物合成基因簇进行分析鉴定。方法对S.costaricanus SCSIO ZS0073菌株进行基因组总DNA提取,利用Highseq4000和PacBio SMRT技术相结合的手段对该菌株进行了基因组完成图测序;利用生物信息学方法对基因组进行注释并寻找fungichromin的生物合成基因簇,对fungichromin生物合成骨架基因fgmJ1进行置换突变,确定fungichromin生物合成基因簇,结合fungichromin结构特征和其基因簇内遗传信息及聚酮化合物的生物合成原理,对其生物合成途径进行推导。结果全基因组测序发现S.costaricanus SCSIO ZS0073菌株基因组含有1条线性染色体和1个环形质粒,基因组含有36个次级代谢产物生物合成基因簇。利用基因敲除手段对fungichromin的生物合成基因簇进行了确认并进行了生物合成途径推导。结论fungichromin生物合成基因簇的确定和生物合成途径的推导为该化合物的基因工程改造研究奠定了分子基础。Objective To obtain the genome information of Stremptomyces costaricanus SCSIO ZS0073 isolated from Hongsha Park（Guangxi,China）and identify the biosynthetic gene cluster responsible for its main product-fungichromin.Methods The genomic DNA of strain S.costaricanus SCSIO ZS0073 was extracted and sequenced using a combination of the second generation Highseq4000 and the third generation PacBio SMRT technology and assembled;the biosynthetic pathway of secondary metabolites was annotated by bioinformatics method.Results Whole genome sequencing revealed that strain S.costaricanus SCSIO ZS0073 contains a linear chromosome as well as a circle plasmid.The antiSMASH annotation results showed that there are 36 secondary metabolites biosynthetic gene clusters in the genome of S.costaricanus SCSIO ZS0073.The gene cluster of fungichromin was identified by bioinformatics analysis and gene inactivation methods.Conclusion The identification of the biosynthetic pathway of fungichromin lays a molecular foundation for future genetic engineering to produce additional antifungal regents.

关 键 词：STREPTOMYCES costaricanus SCSIO ZS0073 fungichromin 生物合成基因簇 基因组分析 

分 类 号：R914[医药卫生—药物化学]