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

通过对产生逆转霉素A的链霉菌的基因簇的鉴定，发现了新的修饰聚酮化合物的酶，有望成为治疗骨质疏松症的候选药物。在基因簇中，发现了催化生物合成反应的酶，该反应将琥珀酸基转移到叔醇。并揭示了该酶在生理环境下进行有机合成的困难反应。本研究旨在通过X-射线晶体结构分析来阐明该酶与该酶的反应机理。通过对结晶条件的探索，得到了酶晶体。并在同步加速器上进行了衍射实验，获得了分辨率为1.8A的衍射数据。通过对所获得的数据进行结构分析的进展，有望在未来弄清楚该酶的结构细节，并阐明其反应机理。

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.