Abstract
The research on antibiotics requires the integration of broad areas, such as microbiology, organic chemistry, biochemistry and pharmacology. It is similar to the field of chemical biology that is recently popular as an approach for drug discovery. When we isolate a new compound from a microorganism, we can pursue the interesting research on chemistry and biology. In this review, I would like to introduce our achievements in relation to reveromycin A.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Waksman, S. A. Antagonistic relations of microorganisms. Bacteriol. Rev. 5, 231–291 (1941).
Osada, H. The Japanese Society for Chemical Biology. ACS Chem. Biol. 1, 8 (2006).
Osada, H. Introduction of new tools for chemical biology research on microbial metabolites. Biosci. Biotechnol. Biochem. 74, 1135–1140 (2010).
Suzuki, S. et al. A new antibiotic, polyoxin. J. Antibiot. 18, 131 (1965).
Endo, A., Kakiki, K. & Misato, T. Mechanism of action of the antifungal agent polyoxin D. J. Bacteriol. 104, 189–196 (1970).
Kuzuhara, H., Ohrui, H. & Emoto, S. Total synthesis of polyoxin J. Tetrahedron. Lett. 14, 5055–5058 (1973).
Osada, H. Development and application of bioprobes for mammalian cell cycle analyses. Curr. Med. Chem. 10, 727–732 (2003).
Osada, H. in Bioprobes (ed. Osada, H.) 1–14 Springer, (2000).
Osada, H. Bioprobes for investigating mammalian cell cycle control. J. Antibiot. 51, 973–982 (1998).
Osada, H., Koshino, H., Isono, K., Takahashi, H. & Kawanishi, G. Reveromycin A, a new antibiotic which inhibits the mitogenic activity of epidermal growth factor. J. Antibiot. 44, 259–261 (1991).
Koshino, H., Takahashi, H., Osada, H. & Isono, K. Reveromycins, new inhibitors of eukaryotic cell growth. III. Structures. J. Antibiot. 45, 1420–1427 (1992).
Takahashi, H. et al. Reveromycins, new inhibitors of eukaryotic cell growth. I. Producing organism, fermentation, isolation and physico-chemical properties. J. Antibiot. 45, 1409–1413 (1992).
Takahashi, H. et al. Reveromycins, new inhibitors of eukaryotic cell growth. II. Biological activities. J. Antibiot. 45, 1414–1419 (1992).
Takahashi, H. et al. Inhibitory action of reveromycin A on TGF-alpha-dependent growth of ovarian carcinoma BG-1 in vitro and in vivo. Oncol. Res. 9, 7–11 (1997).
Woo, J.-T. et al. Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts. Proc. Natl Acad. Sci. USA 103, 4729–4734 (2006).
Cui, Z., Hirata, D., Tsuchiya, E., Osada, H. & Miyakawa, T. The multidrug resistance-associated protein (MRP) subfamily (Yrs1/Yor1) of Saccharomyces cerevisiae is important for the tolerance to a broad range of organic anions. J. Biol. Chem. 271, 14712–14716 (1996).
Miyamoto, Y. et al. Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as target of G1 -specific inhibitor reveromycin A. J. Biol. Chem. 277, 28810–28814 (2002).
Yin, J. J., Pollock, C. B. & Kelly, K. Mechanisms of cancer metastasis to the bone. Cell Res. 15, 57–62 (2005).
Kawatani, M. & Osada, H. Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases. Cancer Sci. 100, 1999–2005 (2009).
Muguruma, H. et al. Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity. Clin. Cancer Res. 11, 8822–8828 (2005).
Yano, A. et al. Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone. Proc. Natl Acad. Sci. USA 105, 15541–15546 (2008).
Umeda, M. et al. Microbial flora in the acute phase of periodontitis and the effect of local administration of minocycline. J. Periodontol. 67, 422–427 (1996).
Tanaka, M. et al. Effect of Reveromycin A on experimental tooth movement in OPG-/- mice. J. Dent. Res. 91, 771–776 (2012).
Yabumoto, T. et al. Stabilization of tooth movement by administration of reveromycin A to osteoprotegerin-deficient knockout mice. Am. J. Orthod. Dentofacial Orthop. 144, 368–380 (2013).
Mizuno, M. et al. Reveromycin A administration prevents alveolar bone loss in osteoprotegerin knockout mice treat periodontal disease. Sci. Rep. 5, 16510 (2015).
Shimizu, T., Kobayashi, R., Osako, K., Osada, H. & Nakata, T. Synthetic studies on reveromycin A: stereoselective synthesis of the spiroketal system. Tetrahedron Lett. 37, 6755–6758 (1996).
Shimizu, T. et al. Synthesis and biological activities of reveromycin A and spirofungin a derivatives. Bioorg. Med. Chem. Lett. 18, 3756–3760 (2008).
Shimizu, T. et al. Chemical modification of reveromycin A and its biological activities. Bioorg. Med. Chem. Lett. 12, 3363–3366 (2002).
Takahashi, S. et al. Reveromycin A biosynthesis uses RevG and RevJ for stereospecific spiroacetal formation. Nat. Chem. Biol. 7, 461–468 (2011).
Oliynyk, M. et al. Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Mol. Microbiol. 49, 1179–1190 (2003).
Gallimore, A. R. et al. Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis. Chem. Biol. 13, 453–460 (2006).
Li, W., Ju, J., Rajski, S. R., Osada, H. & Shen, B. Characterization of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatus unveiling new insights into dialkylmaleic anhydride and polyketide biosynthesis. J. Biol. Chem. 283, 28607–28617 (2008).
Takahashi, S. et al. Structure-function analyses of cytochrome P450revI involved in reveromycin A biosynthesis and evaluation of the biological activity of its substrate, reveromycin T. J. Biol. Chem. 289, 32446–32458 (2014).
Nogawa, T. et al. Creation of novel reveromycin derivatives by alcohol-added fermentation. J. Antibiot. (Tokyo) 66, 247–250 (2013).
Muroi, M. et al. Application of proteomic profiling based on 2D-DIGE for classification of compounds according to the mechanism of action. Chem. Biol. 17, 460–470 (2010).
Futamura, Y. et al. Morphobase, an encyclopedic cell morphology database, and its use for drug target identification. Chem. Biol. 19, 1620–1630 (2012).
Futamura, Y. et al. Identification of a molecular target of a novel fungal metabolite, pyrrolizilactone, by phenotypic profiling systems. Chembiochem 14, 2456–2463 (2013).
Futamura, Y., Muroi, M. & Osada, H. Target identification of small molecules based on chemical biology approaches. Mol. Biosyst. 9, 897–914 (2013).
Acknowledgements
I thank my collaborators for their great efforts, especially, K Isono for his helpful guidance at the beginning of this project. I acknowledge H Takahashi, H Koshino and M Ubukata (now Hokkaido Univ) for the isolation and structural determination of reveromycin A. Regarding the biological studies of reveromycin A, the collaborations with T Miyakawa (Hiroshima Univ), JT Woo, K Nagai (Chubu Univ), S Sone (Tokushima Univ), L Neckers (NCI), S Nagano (Tottori Univ), K Miyazawa and S Goto (Aichi-Gakuin Univ) were indispensable. I also thank T Usui (now Tsukuba Univ), N Kanoh (now Tohoku Univ), T Shimizu and T Nakata for the chemical studies of reveromycin A. I express my gratitude to the current members of our laboratory, particularly T Nogawa, M Kawatani and S Takahashi, for their contributions to the reveromycin study. I express my sincere thanks to the editorial office for giving me a chance to write this review article that is based on the award lecture for the Inhoffen Medal (23 April 2015), delivered in Braunschweig, Germany. I also thank the Helmholtz Centre for Infection Research and the Technical University Braunschweig for awarding me the Inhoffen Medal 2015. The research on reveromycin was supported by the MEXT Grant-in-Aid for Creative Scientific Research, JSPS KAKENHI and the Science and Technology Research Promotion Program for Agriculture, Forestry, Fishery and Food Industry.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no conflict of interest.
Rights and permissions
About this article
Cite this article
Osada, H. Chemical and biological studies of reveromycin A. J Antibiot 69, 723–730 (2016). https://doi.org/10.1038/ja.2016.57
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ja.2016.57
This article is cited by
-
Studies on Streptomyces sp. SN-593: reveromycin biosynthesis, β-carboline biomediator activating LuxR family regulator, and construction of terpenoid biosynthetic platform
The Journal of Antibiotics (2022)
-
Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase
Nature Communications (2021)
