Elucidation of succinyl transferase reaction mechanisms which is difficult to perform by organic synthesis

通过对链霉菌属的基因簇的鉴定，发现了新的修饰聚酮化合物的酶，该链霉菌属的基因簇产生有望作为抗真菌治疗药物候选物的回复霉素A。在该基因簇中，发现了催化将琥珀酰基转移到叔醇的生物合成反应的酶，揭示了该酶在生理环境下进行有机合成的困难反应。本研究的目的是阐明与这种酶的反应机理的细节，通过X-射线晶体结构分析。通过对结晶条件的探索，获得了酶晶体。在同步辐射装置上进行了衍射实验，获得了分辨率达到1.8A的衍射数据。通过对所得数据进行结构分析，有望在将来弄清酶的结构细节并阐明反应机理。

New enzymes which modify the polyketide compounds have been discovered by the identification of gene cluster of Streptomyces which produce reveromycin A expected as an osteoporotic therapeutic drug candidate. In the gene cluster, the enzyme which catalyzes the biosynthesis reaction that transfers a succinyl group to tertiary alcohol was found. And it is revealed that this enzyme conducts a difficult reaction by organic synthesis under physiological environment. This investigation was intended to elucidate the details of the reaction mechanism with this enzyme by X-ray crystal structure analysis. By the crystallization condition search, the enzyme crystals were obtained. And as the result of the diffraction experiments in synchrotron facility, the diffraction data achieve to 1.8 A resolution was obtained. By the progress of structure analysis of obtained data, it is expected that the details of the structure of the enzyme become clear and the reaction mechanism is elucidate in future.