Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.
Xu, Min1; Wang, Yemin1; Zhao, Zhilong2; Gao, Guixi1; Huang, Sheng-Xiong3; Kang, Qianjin1; He, Xinyi1; Lin, Shuangjun1; Pang, Xiuhua2; Deng, Zixin1; Tao, Meifeng1
2016-10-01
Source PublicationAPPLIED AND ENVIRONMENTAL MICROBIOLOGY
Volume82Issue:19Pages:5795-5805
AbstractGenome sequencing projects in the last decade revealed numerous cryptic biosynthetic pathways for unknown secondary metabolites in microbes, revitalizing drug discovery from microbial metabolites by approaches called genome mining. In this work, we developed a heterologous expression and functional screening approach for genome mining from genomic bacterial artificial chromosome (BAC) libraries in Streptomyces spp. We demonstrate mining from a strain of Streptomyces rochei, which is known to produce streptothricins and borrelidin, by expressing its BAC library in the surrogate host Streptomyces lividans SBT5, and screening for antimicrobial activity. In addition to the successful capture of the streptothricin and borrelidin biosynthetic gene clusters, we discovered two novel linear lipopeptides and their corresponding biosynthetic gene cluster, as well as a novel cryptic gene cluster for an unknown antibiotic from S. rochei. This high-throughput functional genome mining approach can be easily applied to other streptomycetes, and it is very suitable for the large-scale screening of genomic BAC libraries for bioactive natural products and the corresponding biosynthetic pathways.
DOI10.1128/AEM.01383-16
Indexed BySCI
Language英语
WOS Research AreaBiotechnology & Applied Microbiology ; Microbiology
WOS SubjectBiotechnology & Applied Microbiology ; Microbiology
WOS IDWOS:000384048700007
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/33613
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Microbial Metab, Shanghai, Peoples R China
2.Shandong Univ, Sch Life Sci, State Key Lab Microbial Technol, Jinan, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, Kunming, Peoples R China
Recommended Citation
GB/T 7714
Xu, Min,Wang, Yemin,Zhao, Zhilong,et al. Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.[J]. APPLIED AND ENVIRONMENTAL MICROBIOLOGY,2016,82(19):5795-5805.
APA Xu, Min.,Wang, Yemin.,Zhao, Zhilong.,Gao, Guixi.,Huang, Sheng-Xiong.,...&Tao, Meifeng.(2016).Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp..APPLIED AND ENVIRONMENTAL MICROBIOLOGY,82(19),5795-5805.
MLA Xu, Min,et al."Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.".APPLIED AND ENVIRONMENTAL MICROBIOLOGY 82.19(2016):5795-5805.
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