Nanaomycin I and J: New nanaomycins generated by mycothiol-mediated compounds from “Streptomyces rosa subsp. notoensis” OS-3966

• Published in: Journal of bioscience and bioengineering Vol. 127; no. 5; pp. 549 - 553
• Main Authors: Matsuo, Hirotaka, Noguchi, Yoshihiko, Také, Akira, Nakanishi, Jun, Shigemura, Katsumi, Sunazuka, Toshiaki, Takahashi, Yōko, Ōmura, Satoshi, Nakashima, Takuji
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.05.2019
• Subjects: Actinomycete; Metabolite; Mycothiol; Nanaomycin I; Nanaomycin J; Streptomyces; Nanaomycin J; Streptomyces; Nanaomycin I; Mycothiol; Metabolite; Actinomycete
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/j.jbiosc.2018.10.013

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.