Study On Bafilomycins,a Secondary Metabolite Produced By Streptomyces Sp. BAF-0711

In this study, the secondary metabolites of Streptomyces BAF-0711 were isolated to screen compounds with novel structures or new bioactivity.Autophagy plays an important role in the process of tumor growth and blocking this process will be helpful for the cancer therapy. Currently,the screening of autophagy inhibitor for antitumor drugs has become a hot spot in anti-tumor drugs research. In our researching work, a compound with anti-tumor bioactivity in the fermentation broth produced by Streptomyces BAF-0711 was found. The TLC results indicated that the active component could be a macrolide. Because of the low fermentation titer, natural selection and orthogonal design were used to increase the titer of target compound to 235.3mg/L. Serial processes were used to get the pure target compound such as macroporous resin column chromatography, silica gel chromatography, C18 chromatography, Sephadex LH-20 gel column chromatography, etc. The chemical structures of the compound were identified to be the macrolide antibiotic bafilomycin A1 by UV, IR, MS and NMR spectra. MTT assay showed that BAF-0711-A has strong growth inhibitory activity compared with lapatinib on MDA-MB-453 cell, with a IC50 value of 0.217 ?mol/mL.Studies show that BAF-0711-A has a wide range of biological activities. As a autophagy inhibitor, BAF-0711-A could be a lead compound as antitumor drug. The yield of BAF-0711-A was increased and reached the industrial level after experiments including natural selection and optimization of fermentation conditions.