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.
Keywords: Chromophore-guided fractionation; DNA topoisomerase inhibitors; Streptomyces sp. LZ35; p-Terphenyl O-β-glucuronides.
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