Cell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Demuris Ltd, Newcastle Biomedicine Bioincubators, William Leech Building, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
J Cell Sci. 2017 Sep 15;130(18):3173-3185. doi: 10.1242/jcs.194571. Epub 2017 Aug 3.
This study was designed to identify bioactive compounds that alter the cellular shape of the fission yeast by affecting functions involved in the cell cycle or cell morphogenesis. We used a multidrug-sensitive fission yeast strain, SAK950 to screen a library of 657 actinomycete bacteria and identified 242 strains that induced eight different major shape phenotypes in These include the typical cell cycle-related phenotype of elongated cells, and the cell morphology-related phenotype of rounded cells. As a proof of principle, we purified four of these activities, one of which is a novel compound and three that are previously known compounds, leptomycin B, streptonigrin and cycloheximide. In this study, we have also shown novel effects for two of these compounds, leptomycin B and cycloheximide. The identification of these four compounds and the explanation of the phenotypes in terms of their known, or predicted bioactivities, confirm the effectiveness of this approach.
本研究旨在通过影响细胞周期或细胞形态发生相关功能来鉴定改变裂殖酵母细胞形状的生物活性化合物。我们使用多药敏感的裂殖酵母菌株 SAK950 来筛选 657 株放线菌文库，并鉴定出 242 株能诱导八种不同主要形态表型的菌株。这些表型包括典型的细胞周期相关的伸长细胞表型和与细胞形态相关的圆形细胞表型。作为原理验证，我们纯化了其中四种活性物质，其中一种是新化合物，三种是先前已知的化合物，即莱普霉素 B、链黑菌素和环己亚胺。在这项研究中，我们还展示了两种化合物莱普霉素 B 和环己亚胺的新作用。这四种化合物的鉴定以及根据其已知或预测的生物活性对表型的解释，证实了这种方法的有效性。
