The zinc bound form of the actinomycete derived natural product compound JBIR-141 induces a mitotic phenotype in fission yeast

This study was designed to identify the natural product compound produced by the actinomycete strain "S149" which is capable of inducing a strong small cell phenotype, called wee, in the fission yeast Schizosaccharomyces pombe. We purified the bioactive molecule, which, on the basis of mass spectrometry data, was identified as a novel zinc-bound form of the previously published molecule JBIR-141. JBIR-141 was not previously known to be a zincophore and does not possess structural features common to other bacterial zinc-binding natural product compounds. Testing the effect of the Zn²⁺ bound form of JBIR-14 against a series of S. pombe deletion mutants which express a wee phenotype suggested its potential target in fission yeast is either Pyp1, which is involved in regulation of the onset of mitosis, an important control in the eukaryotic cell cycle, or an element in the Pyp1 signalling pathway.