title: p-Terphenyl O-β-glucuronides, DNA topoisomerase inhibitors from Streptomyces sp. LZ35ΔgdmAI.
abstract: The analysis of genome sequence indicated that Streptomyces sp. LZ35 has the potential of producing many types of secondary metabolites, including p-terphenyls and geldanamycins. The fermentation of LZ35 in laboratory produces geldanamycins as the major components, which hampers the isolation of minor compounds. To clean the background of geldanamycins, the mutant strain LZ35ΔgdmAI of Streptomyces sp. LZ35 was constructed by disrupting the first PKS module of geldanamycin gene cluster (gdm). From this mutant, five novel p-terphenyls bearing glucuronic acid moiety, namely echosides A-E (1-5), were isolated with the aid of chromophore-guided fractionation. The structures of 1-5 were elucidated by the analysis of their HR-ESI-MS and NMR spectroscopic data. DNA relaxation assay indicated that compound 1 had evident inhibitory activity against topoisomerase I. Moreover, the inhibitory activity of compound 3 against topoisomerase IIα is approximately equal to VP16, indicating that p-terphenyl O-β-glucuronides are promising leads for the development of novel inhibitors of topoisomerases.
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors: Jingjing
authors: J
authors: Deng
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors: Chunhua
authors: C
authors: Lu
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors: Shanren
authors: S
authors: Li
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors: Huilin
authors: H
authors: Hao
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors: Zhenyu
authors: Z
authors: Li
authors: School of Life Sciences, Shandong University, No. 27 South Shanda Road, Jinan, Shandong 250100, PR China.
authors: Jing
authors: J
authors: Zhu
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors: Yaoyao
authors: Y
authors: Li
authors: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, PR China; School of Life Sciences, Shandong University, No. 27 South Shanda Road, Jinan, Shandong 250100, PR China. Electronic address: yshen@sdu.edu.cn.
authors: Yuemao
authors: Y
authors: Shen
mesh_terms: D001665:Binding Sites; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D020719:Glucuronides / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism; D013730:Terphenyl Compounds / Q000737:chemistry*; D059003:Topoisomerase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D020719:Glucuronides; D013730:Terphenyl Compounds; D059003:Topoisomerase Inhibitors; D004264:DNA Topoisomerases, Type I
keywords: Chromophore-guided fractionation; DNA topoisomerase inhibitors; Streptomyces sp. LZ35; p-Terphenyl O-β-glucuronides