Arid
DOI10.1016/j.chembiol.2008.10.006
Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii
Wang, Shuhao1; Xu, Yuquan1; Maine, Erin A.1; Wijeratne, E. M. Kithsiri1; Espinosa-Artiles, Patricia1; Gunatilaka, A. A. Leslie1,2; Molnar, Istvan1,2
通讯作者Molnar, Istvan
来源期刊CHEMISTRY & BIOLOGY
ISSN1074-5521
EISSN1879-1301
出版年2008
卷号15期号:12页码:1328-1338
英文摘要

Fungal polyketides with the resorcylic acid lactone (RAL) scaffold are of interest for growth stimulation, the treatment of cancer, and neurodegenerative diseases. The RAL radicicol is a nanomolar inhibitor of the chaperone Hsp90, whose repression leads to a combinatorial blockade of cancer-causing pathways. Clustered genes for radicicol biosynthesis were identified and functionally characterized from the endophytic fungus Chaetomium chiversii, and compared to recently described RAL biosynthetic gene clusters. Radicicol production is abolished upon targeted inactivation of a putative cluster-specific regulator, or either of the two polyketide synthases that are predicted to collectively synthesize the radicicol polyketide core. Genomic evidence supports the existence of flavin-dependent halogenases in fungi: inactivation of such a putative halogenase from the C. chiversii radicicol locus yields dechloro-radicicol (monocillin I). Inactivation of a cytochrome P450 epoxidase furnishes pochonin D, a deepoxy-dihydro radicicol analog.


类型Article
语种英语
国家USA
收录类别SCI-E
WOS记录号WOS:000262089600011
WOS关键词FUNGAL POLYKETIDE SYNTHASE ; DOUBLE-BOND FORMATION ; GIBBERELLA-ZEAE ; GENE-CLUSTER ; POCHONIA-CHLAMYDOSPORIA ; MOLECULAR CHAPERONE ; CARRIER PROTEIN ; SONORAN-DESERT ; IDENTIFICATION ; HALOGENATION
WOS类目Biochemistry & Molecular Biology
WOS研究方向Biochemistry & Molecular Biology
来源机构University of Arizona
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/156818
作者单位1.Univ Arizona, SW Ctr Nat Prod Res & Commercializat, Off Arid Lands Studies, Tucson, AZ 85706 USA;
2.Univ Arizona, Inst Bio5, Tucson, AZ 85721 USA
推荐引用方式
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Wang, Shuhao,Xu, Yuquan,Maine, Erin A.,et al. Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii[J]. University of Arizona,2008,15(12):1328-1338.
APA Wang, Shuhao.,Xu, Yuquan.,Maine, Erin A..,Wijeratne, E. M. Kithsiri.,Espinosa-Artiles, Patricia.,...&Molnar, Istvan.(2008).Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii.CHEMISTRY & BIOLOGY,15(12),1328-1338.
MLA Wang, Shuhao,et al."Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii".CHEMISTRY & BIOLOGY 15.12(2008):1328-1338.
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