This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a“rounded”or“small”cellular morpholog...This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a“rounded”or“small”cellular morphological phenotype.Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain,SAK950 showed that many induced a“rounded”phenotype.We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes.We show that five of the strains produced streptothricin and that 26 strains produced polyenes,including fungichromin,filipin and candicidin,the last of which was produced by 24 strains.A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S.albidoflavus whilst those that additionally produced streptothricin were related to S.enissocaesilis.A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern.The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S.pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.展开更多
基金the Francis Crick Institute which receives its core funding from Cancer Research UK(FC001121)the UK Medical Research Council(FC001121)+2 种基金the Wellcome Trust(FC001121)In addition,this work was supported by a Wellcome Trust grant to P.N.(Grant Number 093917)Demuris Ltd.
文摘This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a“rounded”or“small”cellular morphological phenotype.Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain,SAK950 showed that many induced a“rounded”phenotype.We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes.We show that five of the strains produced streptothricin and that 26 strains produced polyenes,including fungichromin,filipin and candicidin,the last of which was produced by 24 strains.A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S.albidoflavus whilst those that additionally produced streptothricin were related to S.enissocaesilis.A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern.The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S.pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.
