Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus glarea lozoyensis
文献类型：期刊论文
| 作者 | Chen,Li1,2; Yue,Qun1; Zhang,Xinyu1; Xiang,Meichun1; Wang,Chengshu3; Li,Shaojie1; Che,Yongsheng4; Ortiz-López,Francisco Javier5; Bills,Gerald F5,6; Liu,Xingzhong1 |
| 刊名 | Bmc genomics
 |
| 出版日期 | 2013-05-20 |
| 卷号 | 14期号:1 |
| ISSN号 | 1471-2164 |
| DOI | 10.1186/1471-2164-14-339 |
| 通讯作者 | Liu,xingzhong(liuxz@im.ac.cn) ; An,zhiqiang(zhiqiang.an@uth.tmc.edu) |
| 英文摘要 | Abstractbackgroundthe antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin b0, a lipohexapeptide produced by the fungus glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. the nonribosomal peptide synthetase (nrps)-polyketide synthases (pks) gene cluster responsible for pneumocandin biosynthesis from g. lozoyensis has not been elucidated to date. in this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the g. lozoyensis wild-type strain atcc 20868.resultsthe pneumocandin biosynthetic gene cluster contains a nrps (glnrps4) and a pks (glpks4) arranged in tandem, two cytochrome p450 monooxygenases, seven other modifying enzymes, and genes for l-homotyrosine biosynthesis, a component of the peptide core. thus, the pneumocandin biosynthetic gene cluster is significantly more autonomous and organized than that of the recently characterized echinocandin b gene cluster. disruption mutants of glnrps4 and glpks4 no longer produced the pneumocandins (a0 and b0), and the δglnrps4 and δglpks4 mutants lost antifungal activity against the human pathogenic fungus candida albicans. in addition to pneumocandins, the g. lozoyensis genome encodes a rich repertoire of natural product-encoding genes including 24 pkss, six nrpss, five pks-nrps hybrids, two dimethylallyl tryptophan synthases, and 14 terpene synthases.conclusionscharacterization of the gene cluster provides a blueprint for engineering new pneumocandin derivatives with improved pharmacological properties. whole genome estimation of the secondary metabolite-encoding genes from g. lozoyensis provides yet another example of the huge potential for drug discovery from natural products from the fungal kingdom. |
| 语种 | 英语 |
| WOS记录号 | BMC:10.1186/1471-2164-14-339 |
| 出版者 | BioMed Central |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2374297 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Liu,Xingzhong; An,Zhiqiang |
| 作者单位 | 1.State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences 2.University of Chinese Academy of Sciences 3.Chinese Academy of Sciences; Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant physiology and Ecology, Shanghai Institutes for Biological Sciences 4.Beijing Institute of Pharmacology & Toxicology 5.Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía 6.University of Texas Health Science Center at Houston; Texas Therapeutics Institute, the Brown Foundation Institute of Molecular Medicine |
| 推荐引用方式 GB/T 7714 | Chen,Li,Yue,Qun,Zhang,Xinyu,et al. Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus glarea lozoyensis[J]. Bmc genomics,2013,14(1). |
| APA | Chen,Li.,Yue,Qun.,Zhang,Xinyu.,Xiang,Meichun.,Wang,Chengshu.,...&An,Zhiqiang.(2013).Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus glarea lozoyensis.Bmc genomics,14(1). |
| MLA | Chen,Li,et al."Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus glarea lozoyensis".Bmc genomics 14.1(2013). |
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来源：中国科学院大学
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