Microtubulin assembly inhibitors from microorg origin

几种由微管和其他蛋白质组装而成的细胞器在细胞生物学中起着重要作用。细胞中的mt存在于各种各样的情况中，可以单独出现，也可以松散地排列成束，也可以以定义模式的高度有序的数组出现。这些变化可能与mt的不同功能有关。为了了解这些功能，一些天然存在的化合物被用作分子探针。T-1和曲柳素是有效的有丝分裂抑制剂，由于中心体微管组织中心（MTOCs）紊乱，导致海胆卵出现桶状纺锤体。mt也参与了海胆卵的原核融合（PF）。早期文献中很少有关于这一过程的报道，要更好地了解mt的详细作用和性质，需要发现针对PF的新型特异性抑制剂。我们使用一种新的生物测定系统首次系统地寻找可能具有PF抑制活性的微生物产物。在Streptomyces sp. K02388中发现了一种新的γ -pyrone，命名为streptopyrone，对PF具有明显的抑制活性。在一种真菌Curvularia harveyi中发现了一种新的有丝分裂阻遏物，命名为harveynone，并对其结构进行了分析。该化合物有效地抑制了纺锤体的形成，阻止了海胆卵的第一次细胞分裂。这些化合物的作用方式正在研究中。

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.