Matsuo Hirotaka, Noguchi Yoshihiko, Také Akira, Nakanishi Jun, Shigemura Katsumi, Sunazuka Toshiaki, Takahashi Yōko, Ōmura Satoshi, Nakashima Takuji
Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Research Organization for Nano and Life Innovation, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
J Biosci Bioeng. 2019 May;127(5):549-553. doi: 10.1016/j.jbiosc.2018.10.013. Epub 2018 Nov 29.
Two new nanaomycin analogs, nanaomycin I and J, were isolated from a cultured broth of an actinomycete strain, "Streptomyces rosa subsp. notoensis" OS-3966. In our previous study, we have confirmed the occurrence of nanaomycin I (m/z = 482 [M + H]) that lacks a pseudo-disaccharide from the mycothiol of nanaomycin H under same culture condition. In this study, to confirm the structure of nanaomycin I, the strain "S. rosa subsp. notoensis" OS-3966 was re-cultured and the target compound with m/z = 482 [M + H] was isolated. Furthermore, we discovered another new analog, designated as nanaomycin J in isolating nanaomycin I. The NMR analyses revealed that the structures of nanaomycin I and J are N-acetylcysteine S-conjugates without a pseudo-disaccharide and N-acetylcysteine S-conjugates without a myo-inositol of nanaomycin H, respectively. The relative configurations of the tetrahydropyrane moiety of nanaomycin I and J were determined by rotating-frame overhauser effect spectroscopy (ROESY) analysis. Absolute configurations of the N-acetylcysteine moiety of nanaomycin I and J were determined by advanced Marfey's analyses for acid hydrolysis of de-sulfurized nanaomycin I and J with Raney nickel. Nanaomycin I and J showed moderate cytotoxicity against several human tumor cell lines.
从放线菌菌株“玫瑰链霉菌诺托亚种”OS - 3966的培养液中分离出两种新的纳那霉素类似物，即纳那霉素I和J。在我们之前的研究中，我们已证实在相同培养条件下，纳那霉素I（m/z = 482 [M + H]）存在，它缺少纳那霉素H的硫醇中假二糖结构。在本研究中，为确定纳那霉素I的结构，对“玫瑰链霉菌诺托亚种”OS - 3966菌株进行了再培养，并分离出了m/z = 482 [M + H]的目标化合物。此外，在分离纳那霉素I的过程中，我们发现了另一种新的类似物，命名为纳那霉素J。核磁共振分析表明，纳那霉素I和J的结构分别是不含假二糖的N - 乙酰半胱氨酸S - 共轭物以及不含纳那霉素H的肌醇的N - 乙酰半胱氨酸S - 共轭物。通过旋转框架奥弗豪泽效应光谱（ROESY）分析确定了纳那霉素I和J的四氢吡喃部分的相对构型。通过用阮内镍对脱硫后的纳那霉素I和J进行酸水解的高级马尔菲分析确定了纳那霉素I和J的N - 乙酰半胱氨酸部分的绝对构型。纳那霉素I和J对几种人类肿瘤细胞系显示出中等程度的细胞毒性。
