Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast

This study was designed to identify bioactive compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe 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 S. pombe. 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 S. pombe phenotypes in terms of their known, or predicted bioactivities, confirm the effectiveness of this approach.