Natural Products and Bioprospecting ( IF 4.8 ) Pub Date : 2021-04-21 , DOI: 10.1007/s13659-021-00304-1 Richard Alexander Lewis 1 , Jenileima Devi 1 , Katherine Green 1 , Juanjuan Li 2 , Adam Hopkins 1 , Jacqueline Hayles 3 , Paul Nurse 3 , Jeff Errington 1 , Nicholas Edward Ellis Allenby 1
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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.
Graphic Abstract
中文翻译：
诱导裂殖酵母“圆形”形态表型的放线菌天然产物的筛选和纯化
本研究旨在鉴定和研究具有生物活性的天然产物化合物，这些化合物可以改变裂殖酵母裂殖酵母的细胞形状并诱导“圆形”或“小”细胞形态表型。使用一系列抗真菌剂针对多药敏感的裂殖酵母菌株 SAK950 进行的生物测定表明，许多抗真菌剂可诱导“圆形”表型。然后，我们研究了我们之前的研究中鉴定出的 46 种放线菌菌株是否诱导相似的表型产生相似类别的抗真菌药物。我们发现其中 5 个菌株产生链丝菌素，26 个菌株产生多烯，包括真菌染色蛋白、菲律宾素和念珠菌素，其中最后一个菌株由 24 个菌株产生。对菌株的分类学研究表明，大多数仅产生念珠菌素的菌株是氢链霉菌和白黄链霉菌，而另外产生链丝菌素的菌株则与链霉菌有关。一项调查相关菌株产生的天然产物的后续研究表明，它们遵循类似的模式。从放线菌菌株中鉴定出与最初测试的抗真菌剂相似的几种化合物，证实了使用粟酒裂殖酵母形态表型和放线菌分类学作为天然产物鉴定的预测工具的方法的有效性。
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