Microtubulin assembly inhibitors from microorg origin

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Several cell organelles assembled from microtubules (MTs) and other proteins perform an important role in cell biology. MTs are found in a great variety of situations in cells, and may occur singly, loosely ordered into bundles, or in highly ordered arrays of a define pattern. These variations are presumably related to the different functions of MTs. In order to understand such functions, several naturally occurring compounds have been used as molecular probes. T-1 and curvularin have been found to be effective mitotic inhibitors which induced barrel-shaped spindles in sea urchin eggs due to disorder of the microtubule organising centers ( MTOCs) in centrosomes. MTs are also involved in the pronuclear fusion (PF) of sea urchin eggs. Early literature contains few reports of this process, and a better understanding of the detailed role and nature of MTs awaits the discovery of new types of specific inhibitors toward PF. We made the first systematic search for microbial products that might have PF inhibitory activity using a novel bioassay system. A Streptomyces sp. K02388 was discovered, which produced a novel gamma-pyrone, named streptopyrone with pronounced inhibitory activity toward PF. A fungus, Curvularia harveyi, was found to produce a new mitotic arrester, which was named harveynone and its structure was elucidated. This compound effectively inhibited spindle formation and arrested the first cell division of sea urchin eggs. The mode of operation of these compounds are in progress.