Biomolecular-chemical screening: A novel screening approach for the discovery of biologically active secondary metabolites - III. New DNA-binding metabolites

Based on the chemical screening technique, biomolecular-chemical screening has been developed which makes use of two-dimensional TLC analysis of micro bial extracts and combines thin-layer chromatography (RP-18) with binding s tudies towards DNA. In the first dimension the metabolites of the crude mic robial extract are separated, and in the second dimension binding propertie s towards DNA are analysed. An initial screening program with 500 microbial extracts prepared by solid-phase extraction with XAD-16 resin resulted in 17 samples which contained metabolites with significant DNA-binding behavio r. Fermentation, isolation and structural characterization led to already k nown metabolites [phenazine-1,6-dicarboxylate (1), phencomycin (2), 11-carb oxy-menoxymycin B (3), soyasaponine I (4), and (8S)-3-(2-hydroxypropyl)-cyc lohexanone (5)], as well as to new secondary metabolites. Fermentation of t he producing organisms of the new DNA-binding metabolites, ent-8,8a-dihydro -ramulosin (6), (2R,4R)-4-hydroxy-2-(1,3-pentadienyl)-piperidine (7), (5R)- dihydro-5-pentyl-4'-methyl-4'-hydroxy-2(3H)-furanone (8), and seco-4,23-hyd roxyoleane-13-en-22-one-3-carboxylic acid (9), as well as isolation, struct ural characterization, and physico-chemical properties are reported.