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

Abstract

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, Elongated cells and cell morphology related phenotype Rounded cells. As a proof of principle we purified four of these activities, one of which is a novel compound and three that are the 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.