Biological Systems Control Team





医薬品をはじめとする、生理活性物質に関する研究を行ないます。

種々の疾患ターゲットを指標としたアッセイ系を構築し、主に微生物代謝産物を対象にスクリーニングを行ないます。
また、ターゲット分子の同定などを介して、化合物の活性発現メカニズムの解明を行ないます。









・世界最大の天然物ライブラリーの確立。
・大規模な天然物スクリーニングシステムの確立と第二世代天然物化学の展開。
・LC-NMR-MS・LC-MS等を用いた迅速な化合物同定システムの確立。
・多様な有用生理活性物質の単離。

2009

Role of TLS DNA polymerases eta and kappa in processing naturally occurring structured DNA in human cells. Mol. Carcinog. 48(4), 369-378. R. Bétous, L. Rey, G.Wang, M.-J. Pillaire, N. Puget, J. Selves, D. S. Biard, K. Shin-ya, K. M. Vasquez, C. Cazaux, J.-S. Hoffmann.

Preventing the unfolded protein response via aberrant activation of 4E-binding protein 1 by versipelostatin. Cancer Sci. 100(2), 327-333. J. Matsuo, Y. Tsukumo, J. Sakurai, S. Tsukahara, H.-R. Park, K. Shin-ya, T. Watanabe, T. Tsuruo and A. Tomida.

JBIR-23 and -24, novel anticancer agents from Streptomyces sp. AK-AB27. Org. Lett. 11(2), 285-288. K. Motohashi, J.-H. Hwang, M. Takagi and K. Shin-ya.

Synthesis of a potent G-quadruplex-binding macrocyclic heptaoxazole. Chembiochem. 10, 431-435. M. Tera, K. Iida, H. Ishizuka, M. Takagi, M. Suganuma, T. Doi, K. Shin-ya and K. Nagasawa.

Discovery of a pimaricin analog JBIR-13, from Streptomyces bicolor NBRC 12746 as predicted by sequence analysis of type I polyketide synthase gene. Appl. Microbio. Biotechnol. 83(1), 127-133. H. Komaki, M. Izumikawa, J. Ueda, T. Nakashima, S. T. Khan, M. Takagi and K. Shin-ya.

Novel 24-membered macrolides, JBIR-19 and -20 isolated from Metarhizium sp. fE61. J. Antibiot. 62(3), 159-162. I. Kozone, J. Ueda, M. Watanabe, S. Nogami, A. Nagai, S. Inaba, Y. Ohya, M. Takagi and K. Shin-ya.

Ammocidins B, C and D, new cytotoxic 20-membered macrolides from Saccharothrix sp. AJ9571. J. Antibiot. 62(3), 123-127. R. Murakami, J. Shinozaki, T. Kajiura, I. Kozone, M. Takagi, K. Shin-ya, H. Seto and Y. Hayakawa.

Isolation of azaspiracid-2 from a marine sponge Echinoclathria sp. as a potent cytotoxin. Toxicon. 53(6), 680-684. R. Ueoka, A. Ito, M. Izumikawa, S. Maeda, M. Takagi, K. Shin-ya, M. Yoshida, R. W. M. van Soest and S. Matsunaga.

JBIR-12, a novel antioxidative agent from Penicillium sp. NBRC 103941. J. Antibiot. 62(4), 177-180. M. Izumikawa, A. Nagai, T. Doi, M. Takagi and K. Shin-ya.

New glycosylated derivatives of versipelostatin, the GRP78/Bip molecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS6. Org. Biomol. Chem. 7(7), 1454-1460. P. Zhao, J. Ueda, I. Kozone, S. Chijiwa, M. Takagi, F. Kudo, M. Nishiyama, K. Shin-ya and T. Kuzuyama.

Two novel decanedienamide derivatives, JBIR-07 and -08 from Streptomyces versipellis 4083-SVS6. Nat. Prod. Res. 23(14), 1337-1341. J. Ueda, M. Takagi and K. Shin-ya.

Efficient synthesis of deoxysugar part of versipelostatin via direct and stereoselective glycosidation. Chem. Asian J. 4(7), 1114-1125. H. Tanaka, A. Yoshizawa, S. Chijiwa, M. Takagi, K. Shin-ya and T. Takahashi.

A solid-phase total synthesis of the cyclic depsipeptide HDAC inhibitor spiruchostatin A. Tetrahedron Lett. 50(24), 2970-2972. Y. Iijima, A. Munakata, K. Shin-ya, A. Ganesan, T. Doi and T. Takahashi.

JBIR-27 and -28 isolated from tunicate-derived fungus, Penicillium sp. SS080624SCf1. J. Antibiot. 62(5), 247-250. K. Motohashi, J. Hashimoto, S. Inaba, S. T. Khan, H. Komaki, A. Nagai, M. Takagi and K. Shin-ya.

JBIR-17, a novel trichostatin analogue from Streptomyces sp. 26634. J. Antibiot. 62(5), 283-285. J. Ueda, J.-H. Hwang, T. Kato, A. Ochiai, K. Isshiki, M. Takagi and K. Shin-ya.

Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation. Cancer Res. 69(10), 4225-4234. S. Saito, A. Furuno, J. Sakurai, A. Sakamoto, H.-R. Park, K. Shin-ya, T. Tsuruo and A. Tomida.

JBIR-44, a new bromotyrosine compound from a marine sponge Psammaplysilla purpurea. J. Antibiot. 62(7), 393-395. T. Fujiwara, J.-H. Hwang, A. Kanamoto, H. Nagai, M. Takagi and K. Shin-ya.

Paraoerskovia marina gen. nov., sp. nov., an actinobacterium isolated from marine sediment. International Journal of Systematic and Evolutionary Microbiology. 59(8), 2094-2098. S. T. Khan, S. Harayama, T. Tamura, K. Ando, M. Takagi and K. Shin-ya.

JBIR-15, a new aspochracin derivative, isolated from a sponge-derived fungus, Aspergillus sclerotiorum Huber Sp080903f04. Biosci. Biotechnol. Biocem. 73(8), 1898-1900. K. Motohashi, S. Inaba, M. Takagi and K. Shin-ya.

JBIR-37 and -38, novel glycosyl benzenediols, isolated from the sponge-derived fungus, Acremonium sp. SpF080624G1f01. Biosci. Biotechnol. Biocem. 73(9), 2138-2140. M. Izumikawa, S. T. Khan, H. Komaki, A. Nagai, S. Inaba, M. Takagi and K. Shin-ya.

The G-quadruplex ligand telomestatin impairs binding of topoisomerase IIIα to G-quadruplex-forming oligonucleotides and uncaps telomeres in ALT cells. PLoS One. 4(9), e6919. N. Temime-Smaali, L. Guittat, A. Sidibe, K. Shin-ya, C. Trentesaux, J.-François Riou.

Reevaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action. Proc. Natl. Acad. Sci. U S A. 104(44), 17347-17352. A. De Cian, G. Cristofari, P. Reichenbach, E. De Lemos, D. Monchaud, M.-P. Teulade-Fichou, K. Shin-ya, L. Lacroix, J. Lingner and J.-L. Mergny.

2008

Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down-regulator. J. Cell. Physiol. 215(1), 243-250. J.-H. Hwang, J.-Y. Kim, M.-R. Cha, I.-J. Ryoo, S.-J. Choo, S.-M. Cho, Y. Tsukumo, A. Tomida, K. Shin-ya, Y.-I. Hwang, I.-D. Yoo, and H.-R. Park.

A novel antimycin-like compound, JBIR-06, from Streptomyces sp. ML55. J. Antibiot. 61(4), 241-244. J. Ueda, A. Nagai, M. Izumikawa, S. Chijiwa, M. Takagi and K. Shin-ya.

FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability. Mol. Cell Biol. 28(12), 4116-4128. Yuliang Wu, K. Shin-ya and R. M. Brosh, Jr.

Macrocyclic hexaoxazoles as sequence- and mode-selective G-quadruplex binders. Angew. Chem. Int. Ed. 47(30), 5557-5560. M. Tera, H. Ishizuka, M. Takagi, M. Suganuma, K. Shin-ya and K. Nagasawa.

Stawamycin analog, JBIR-11 from Streptomyces viridochromogenes subsp. sulfomycini NBRC13830. J. Antibiot. 61(5), 326-329. M. Izumikawa, H. Komaki, J. Hashimoto, M. Takagi and K. Shin-ya.

Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A. Biochem. Phramacol. 76(4), 463-475. S. J. Crabb, M. Howell, H. Rogers, M. Ishfaq, A. Y.-George, K. Carey, B. M. Pickering, P. East, R. Mitter, S. Maeda, P. W. Johnson, P. Townsend, K. Shin-ya, M. Yoshida, A Ganesan and Graham Packham.

Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp. J. Antibiot. 61(6), 365-371. Y. Hayakawa, Y. Hattori, T. Kawasaki, K. Kanoh, K. Adachi, Y. Shizuri and K. Shin-ya.

Total synthesis of largazole and its biological evaluation. Synlett. 16(6), 2483-2486. Y. Numajiri, T. Takahashi, M. Takagi, K. Shin-ya and T. Doi.

A novel versipelostatin analogue, versipelostatin F isolated from Streptomyces versipellis 4083-SVS6. J. Antibiot. 61(12), 752-755. J. Ueda, S. Chijiwa, M. Takagi and K. Shin-ya.

JBIR-26, a novel natural compound from Streptomyces sp. AK-AH76, regulates mammalian circadian clock. J. Antibiot. 61(12), 756-758. M. Izumikawa, H. Ukai, M. Takagi, H. R. Ueda and K. Shin-ya.

Studying telomere replication by Q-CO-FISH: the effect of telomestatin, a potent G-quadruplex ligand. Cytogenet. and Genome Res. 122(3-4), 229-236. No. 3-4. N. Arnoult, K. Shin-ya and J.-A. Londoño-Vallejo.

2007

Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator. Toxicology. 229(3), 253-261. H.-R. Park, I.-J. Ryoo, S.-J. Choo, J.-H. Hwang, J.-Y. Kim, M.-R. Cha, K. Shin-ya and I.-D. Yoo.

Telomere protection mechanisms change during neurogenesis and neuronal maturation: newly generated neurons are hypersensitive to telomere and DNA damage. J. Neurosci. 27(14), 3722-3733. A. Cheng, K. Shin-ya, R. Wan, S.-C. Tang, T. Miura, H. Tang, R. Khatri, M. Gleichman, X. Ouyang, D. Liu, H.-R. Park, J. Y. Chiang and M. P. Mattson.

Relative and absolute configuration of versipelostatin, a down-regulator of molecular chaperone GRP78 expression. Org. Lett. 9(8), 1457-1460. H.-R. Park, S. Chijiwa, K. Furihata, Y. Hayakawa and K. Shin-ya.

Urukthapelstatin A, a novel cytotoxic substance from Marine-derived Mechercharimyces asporophorigenens YM11-542. I. Fermentation, Isolation and Biological Activities. J. Antibiot. 60(4), 251-255. Y. Matsuo, K. Kanoh, T. Yamori, H. Kasai, A. Katsuta, K. Adachi, K. Shin-ya and Y. Shizuri.

New aureothin derivative, alloaureothin, from Streptomyces sp. MM23. J. Antibiot. 60(5), 321-324. J. Ueda, J. Hashimoto, A. Nagai, T. Nakashima, H. Komaki, K. Anzai, S. Harayama, T. Doi, T. Takahashi, K. Nagasawa, T. Natsume, M. Takagi and K. Shin-ya.

A novel nuclear export inhibitor JBIR-02, a piericidin derivative from Streptomyces sp. ML55. J. Antibiot. 60(7), 459-462. J. Ueda, T. Togashi, S. Matsukura, A. Nagai, T. Nakashima, H. Komaki, K. Anzai, S. Harayama, T. Doi, T. Takahashi, T. Natsume, Y. Kisu, N. Goshima, N. Nomura, M. Takagi and K. Shin-ya.

Absolute Structure of Prunustatin A, a Novel GRP78 Molecular Chaperone Down-Regulator. Org. Lett. 9(21), 4239-4242. Y. Umeda, K. Furihata, S. Sakuda, H. Nagasawa, K. Ishigami, H. Watanabe M. Izumikawa, M. Takagi, T. Doi, Y. Nakao and K. Shin-ya.

Macrocyclic and helical oligoamides as a new class of G-quadruplex ligands. J. Am. Chem. Soc. 129(39), 11890-11891. P. S. Shirude, E. R. Gillies, S. Ladame, F. Godde, K. Shin-ya, I. Huc and S. Balasubramanian.

Novel GRP78 molecular chaperone expression down-regulators JBIR-04 and -05 isolated from Streptomyces violaceoniger. J. Antibiot. 60(10), 640-644. M. Izumikawa, J. Ueda, S. Chijiwa, M. Takagi and K. Shin-ya.

A novel indole-diterpenoid, JBIR-03 with anti-MRSA activity from Dichotomomyces cejpii var. cejpii NBRC 103559. J. Antibiot. 60(10), 645-648. M. Ogata, J. Ueda, M. Hoshi, J. Hashimoto, T. Nakashima, K. Anzai, M. Takagi and K. Shin-ya.

Burkholone, a new cytotoxic antibiotic against IGF-I dependent cells from Burkholderia sp. J. Antibiot. 60(11), 713-716. T. Mori, T. Yamashita, K. Furihata, K. Nagai, K. Suzuki, Y. Hayakawa and K. Shin-ya.

2006

A total synthesis of spiruchostatin A. Tetrahedron Lett. 47(7), 1177-1180. T. Doi, Y. Iijima, K. Shin-ya, A. Ganesan and T. Takahashi.

Selective cytotoxic activity of valinomycin against HT-29 human colon carcinoma cells via down-regulation of GRP78. Biol. Pharm. Bull. 29(4), 817-820. I.-J. Ryoo, H.-R. Park, S.-J. Choo, J.-H. Hwang, Y.-M. Park, K.-H. Bae, K. Shin-ya and I.-D. Yoo.

Total synthesis of (R)-telomestatin. Org. Lett. 8(18), 4165-4167. T. Doi, M. Yoshida, K. Shin-ya and T. Takahashi.

Design and synthesis of telomestatin derivatives and their inhibitory activity of telomerase. Heterocycles. 69(1), 505-514. M. Tera, Y. Sohtome, H. Ishizuka, T. Doi, M. Takagi, K. Shin-ya and K. Nagasawa.