Summary
Bioactive microbial metabolites are attracting increasing attention as useful agents for medicine, veterinary medicine, agriculture, and as unique biochemical tools. A review of the current trends in the discovery-of new metabolites shows that the number of active compounds with non-antibiotic type of activity has increased, resulting in an expansion of the variety of bioactivity of microbial metabolites. Factors that contribute to the increased rate of discovery include: development of new methods for activity measurement, exploitation of novel groups of microorganisms as sources of active compounds, new directions for chemical modification, and incorporation of newer knowledge of biotechnology into screening systems. To exemplify this, typical screening methods, and chemical and biological properties of several bioactive compounds obtained by these methods are discussed.
Similar content being viewed by others
References
Aldridge, D.C., D. Gil and W.B. Turner. 1971. Antibiotic 1233a: a fungal β-lactone. J. Chem. Soc. (C): 3888–3891.
Baldwin, J.E., R.M. Adlington, A. Basak, S.L. Flitsch, S. Petursson, N.J. Turner and H.-H. Ting. 1986. Enzymatic synthesis of a new type of penicillin. J. Chem. Soc., Chem. Commun. 1986: 975–976.
Barde, Y.-A. 1989. Trophic factors and neuronal survival. Neuron 2: 1525–1534.
Bartnicki-Garcia, S. and M.C. Wang. 1983. Biochemical aspects of morphogenesis inPhytophthora. In: Phytophthora: Its Biology, Taxonomy, Ecology, and Pathology (Erwin, D.C. et al., eds.), pp. 121–137, American Phytopathology Society, MN.
Boeck, L.D., D.S. Fukuda, B.J. Abbott and M. Debono. 1989. Deacylation of echinocandin B byActinoplanes utahensis. J. Antibiot. 42: 382–388.
Brown, J.C., M.A. Cook and J.R. Dryburgh. 1973. Motilin, a gastric motor activity stimulating polypeptide: The complete amino acid sequence. Can. J. Biochem. 51: 533–537.
Buchholz, R.A., R.L. Duvdore, W.R. Cumiskey, A.L. Harris and R.J. Silver. 1991. Protein kinase inhibitors and blood pressure control in spontaneously hypertensive rats. Hypertension 17: 91–100.
Burg, R.W., B.M. Miller, E.E. Baker, J. Birnbaum, S.A. Currie, R. Hartman, Y. Kong, R.L Monaghan, G. Olson, I. Putter, J.B. Tunac, H. Wallick, E.O. Stapley, R. Oiwa and S. Ōmura. 1979. Avermectins, new family of potent anthelmintic agents: producing organism and fermentation. Antimicrob. Agents Chemother. 15: 361–367.
Debono, M., B.J. Abbott, D.S. Fukuda, M. Barnhart, K.E. Willard, R.M. Molloy, K.H. Michel, J.R. Turner, T.F. Butler and A.H. Hunt. 1989. Synteesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide: synthesis of the antifungal agent cilofungin (LY 121019). J. Antibiot. 42: 389–397.
Delay-Goyet, P. and J.M. Lundberg. 1991. Dactinomycin is a competitive neurokinin-2 receptor antagonist. Biochem. Biophys. Res. Commun. 180: 1342–1349.
Chen, S.T., O.D. Hensens and M.D. Schulman. 1989. Chapter 4. Biosynthesis. In: Ivermectin and Abamectin (Campbell W.C., ed.), pp. 55–72, Springer-Verlag, New York.
Cole, S.P., B.A.M. Rudd, D.A. Hopwood, C.-J. Chang and H.G. Floss. 1987. Biosynthesis of the antibiotic actinorhodin: analysis of blocked mutants ofStreptomyces coelicolor. J. Antibiot. 40: 340–347.
Delmer, D.P. 1983. Biosynthesis of cellulose. In: Adv. Carbohydrate Chemistry and Biochemistry Vol.41 (Tipson, R.S. and D. Horton, eds.), pp. 105–153, Academic Press, New York.
Depoortere, I., T.L. Peeters and G. Vantrappen. 1990. The erythromycin derivative EM-523 is a potent motilin agonist in man and in rabbit. Peptides 11: 515–519.
Erkel, G. and T. Anke. 1992. Antibiotics from basidiomycetes 41. Clavicoronic acid, a novel inhibitor of reverse transcriptase fromClavicorona pyxidata. J. Antibiot. 45: 29–37.
Fisher, M.H. and H. Mrozik. 1984. The avermectin family of macrolide-like antibiotics. In: Macrolide Antibiotics. Chemistry, Biology and Practice (Ōmura, S., ed.), pp. 553–606, Academic Press, Orlando.
Fujimoto, M., S. Shinagawa, M. Wakimasu, C. Kitada and H. Yajima. 1978. Synthesis of porcine motilin and itsd-Pheanalog by the use of methanesulfonic acid. Chem. Pharm. Bull. 26: 101–107.
Funayama S., Y. Anraku, A. Mita, K. Komiyama and S. Ōmura. 1989. Structural study of isoflavonoids possessing antioxidant activity isolated from the fermentation broth ofStreptomyces sp. J. Antibiot. 42: 1350–1355.
Funayama, S., M. Ishibashi, Y. Anraku, M. Miyauchi, H. Mori, K. Komiyama and S. Ōmura. 1989. Novel cytocidal antibiotics, glucopiericidinols A1 and A2. Taxonomy, fermentation, isolation, structure elucidation and biological characteristics. J. Antibiot. 42: 1734–1740.
Funayama, S., M. Ishibashi, K. Komiyama and S. Ōmura. 1991. A new antibiotic, okicenone. II. Physico-chemical properties and structure elucidation. J. Antibiot. 44: 819–823.
Funayama, S., M. Ishibashi, K. Komiyama and S. Ōmura. 1990. Biosynthesis of furaquinocins A and B. J. Org. Chem. 55: 1132–1133.
Greene, B.M. and H.R. Taylor. 1989. Use of ivermectin in humans. In: Ivermectin and Abamectin (Campbell, W.C., ed.), pp. 311–323, Springer-Verlag, New York.
Haigler, C.H., R.M. Brown Jr. and M. Benziman. 1980. Calcofluor White ST alters the in vivo assembly of cellulose microfibrils. Science 210: 903–906.
Hardie, D.G., T.A.J. Haystead and A.T.R. Sim. 1991. Use of okadaic acid to inhibit protein phosphatase in intact cells. In: Methods in Enzymology Vol. 201. Protein phosphorylation Part B (Hunter, T. and B.M. Sefton, eds.), pp. 469–476, Academic Press, San Diego.
Hartman, E.J., S. Ōmura and M. Laposata. 1989. Triacsin C, a differential inhibitor of arachidonyl-CoA synthetase and nonspecific long chain acyl-CoA synthetase. Prostaglandins 37: 655–671.
Hayakawa, M., T. Kajiura and H. Nonomura. 1991. New methods for the highly selective isolation ofStreptosporangium andDactylosporangium from soil. J. Ferment. Bioeng. 72: 327–333.
Hefti, F.L. and W.J. Weiner. 1986. Nerve growth factors and Alzheimer's disease. Ann. Neurol. 20: 275–281.
Heim, D.R., J.R. Skomp, E.E. Tschabold and I.M. Larrinua. 1990. Isoxaben inhibits the synthesis of acid insoluble cell wall materials inArabidops thaliana. Plant Physiol. 93: 695–700.
Hopwood, D.A. 1990. Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annu. Rev. Genet. 24: 37–66.
Hopwood, D.A., F. Malpartida, H.M. Kieser, H. Ikeda, J. Duncan, I. Fujii, B.A.M. Rudd, H.G. Floss and S. Ōmura. 1985. Production of hybrid antibiotics by genetic engineering. Nature (Lond.) 312: 642–644.
Horinouchi, S., F. Malpartida, D.A. Hopwood and T. Beppu. 1989.afs B stimulates transcription of the actinorhodin biosynthesis pathway inStreptomyces coelicolor A3(2) andStreptomyces lividans. Mol. Gen. Genet. 215: 355–357.
Horinouchi, S., K. Miyake, S.-K. Hong, D. Vujaklija, K. Ueda and T. Beppu. 1991. Regulation by A-factor andafs R of secondary metabolism and morphogenesis. Actinomycetologica (Tokyo) 5: 119–125.
Ikeda, H. and S. Ōmura. 1991. Strategic strain improvement of antibiotic producer. Actinomycetologica (Tokyo) 5: 86–99.
Ikeda, H. and S. Ōmura. 1991. Genetics of antibioticproducingStreptomyces. Kitasato Arch. Exp. Med. 63: 143–155.
Ikeda, H., H. Kotaki and S. Ōmura. 1987. Genetic studies of avermectin biosynthesis inStreptomyces avermitilis. J. Bacteriol. 169: 5615–5621.
Imamura, N., H. Kuga, K. Otoguro, H. Tanaka and S. Ōmura. 1989. Structures of jietacins: unique α, β-unsaturated azoxy antibiotics. J. Antibiot. 42: 156–158.
Inaoka, Y., H. Tamaoki, S. Takahashi, R. Enokita and T. Okazaki. 1986. Propioxatins A and B, new enkephalinase B inhibitors. I. Taxonomy, fermentation, isolation and biological properties. J. Antibiot. 39: 1368–1377.
Inatomi, N., H. Satoh, Y. Maki, N. Hashimoto, Z. Itoh and S. Ōmura. 1989. An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs. J. Pharmacol. Exp. Ther. 251: 707–712.
Ingber, D., T. Fujita, S. Kishimoto, K. Sudo, T. Kanamaru, H. Brem and J. Folkman. 1990. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumor growth. Nature 348: 555–557.
Inokoshi, J., H. Takeshima, H. Ikeda and S. Ōmura. 1992. Cloning and sequencing of the aculeacin A acylase gene fromActinoplanes utahensis and its expression inStreptomyces lividans. Gene (in press).
Ishihara, N., M. Iwama and B. Kobayashi. 1989. Stabilization of blood platelet microtubular system by staurosporine. Life Sci. 44: 1309–1316.
Itoh, Z., S. Takeuchi, I. Aizawa and T. Takayanagi. 1978. Characteristics notor activity of the gastrointestinal tract in fasted conscious dogs measured by implanted force transducers. Am. J. Dig. Dis. 23: 229–238.
Itoh, Z., T. Suzuki, M. Nakaya, Y. Inoue and S. Mitsuhashi. 1984. Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut. Antimicrob. Agents Chemother. 26: 863–869.
Iwai, Y., A. Nakagawa, N.Sadakane, S. Ōmura, H. Oiwa, S. Matsumoto, M. Takahashi, T. Ikai and Y. Ochiai. 1980. Herbimycin B, a new benzoquinoid ansamycin with anti-TMV and herbicidal activites. J. Antibiot. 33: 1114–1119.
Kakinuma, S., H. Ikeda and S. Ōmura. 1991. Genetic studies of the biosynthesis of kalafungin, a benzoisochromanequinone antibiotic. Tetrahedron 47: 6059–6068.
Kamiryo, T., Y. Nishikawa, M. Mishina, M. Terao and S. Numa. 1979. Involvement of long-chain acyl coenzyme A for lipid synthesis in repression of acyl-coenzyme A carboxylase inCandida albicans. Proc. Natl. Acad. Sci. USA 76: 4390–4394.
Kaneko, H., T. Sasaki, N.S. Ramamurthy and L.M. Golub. 1990. Tetracycline administration normalizes the structure and acid phosphatase activity of osteoclasts in streptozotocin-induced diabetic rats. Anatom. Rec. 227: 427–436.
Khan, N., A. Graslund, A. Ehrenberg and J. Shriver. 1990. Sequence-specific1H-NMR assignments and secondary structure of porcine motilin. Biochemistry 29: 5743–5751.
Kirsch, D.R., M.H. Lai, J. McCullough and A.M. Gillum. 1991. The use of β-galactosidase gene fusions to screen for antibacterial antibiotics. J. Antibiot. 44: 210–217.
Kirst, H.A., K.E. Willard, M. Debono, J.E. Toth, B.A. Truedell, J.P. Leeds, J.L. Ott, A.M. Felty-Duckworth, F.T. Counter, E.E. Ose, G.D. Grouse, J.M. Tustin and S. Ōmura. 1989. Structure-activity studies of 20-deoxo-20-amino derivatives of tylosin-related macrolides. J. Antibiot. 42: 1673–1683.
Kishore, G.M. and D.M. Shah. 1988. Amino acid biosynthesis inhibitors as herbicides. Annu. Rev. Biochem. 57: 627–663.
Komiyama, K., K. Okada, Y. Hirokawa, K. Masuda, S. Tomisaka and I. Umezawa. 1985. Antitumor activity of a new antibiotic, kazusamycin. J. Antibiot. 38: 224–229.
Komiyama, K., S. Funayama, Y. Anraku, M. Ishibashi, Y. Takahashi and S. Ōmura. 1990. Novel antibiotics, furaquinocins A and B. Taxonomy, fermentation, isolation and physico-chemical and biological characteristics. J. Antibiot. 43: 247–252.
Kondo, Y., K. Torii, S. Ōmura and Z. Itoh. 1988. Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of125I-motilin to duodenal muscle. Biochem. Biophys. Res. Commun. 150: 877–882.
Konishi, M. and T. Oki. 1991. A novel class of antitumor antibiotics containing a cyclodiyne skeleton: activity and mechanism of action. Actinomycetologica (Tokyo) 5: 1–9.
Kuder H.V. 1960. Propionyl erythromycin. A review of 20525 case reports for side effect data. Clin. Pharmacol. Ther. 1: 604–609.
Kumagai, H., H. Nishida, N. Imamura, H. Tomoda and S. Ōmura. 1990. The structure of atpenins A4, A5 and B, new antifungal antibiotics produced byPenicillium sp. J. Antibiot. 43: 1553–1558.
Kunze, B., W. Trowitzsch-Kienast, G. Hoefle and H. Reichenbach. 1992. Nannochelins A, B and C, new ion-chelating compounds fromNannocystis exedens (Myxobacteria). Production, isolation, physico-chemical and biological properties. J. Antibiot. 45: 147–150.
Kurisaki, T., J. Magae, K. Isono, K. Nagai and M. Yamasaki. 1992. Effect of tautomycin, a protein phosphatase inhibitor, on recycling of mammalian cell surface molecules. J. Antibiot. 45: 252–257.
Lechevalier, M.P. and H. Lechevalier. 1970. Chemical composition as a criterion in the classification of aerobic actinomycetes. Int. J. Syst. Bacteriol. 20: 435–443.
Maeda, M., T. Kodama, N. Iwasawa, N. Higuchi and N. Amano. 1989. Production of aspartic proteinase inhibitors byKitasatosporia kyotoensis. European Patent Application 0316, 907 A2.
Matthews, H.W. and B.F. Wade. 1977. Pharmacologically active compounds from microbial origin. Adv. Appl. Microbiol. 21: 269–288.
McGuire, J.M., R.L. Bunch, R.C. Anderson, H.E. Boaz, E.H. Flyan, H.M. Powell and J.W. Smith. 1952. Ilotycin, a new antibiotic. Antibiot. Chemother. 2: 281–283.
Mizuno, K., A. Yagi, S. Satoi, M. Takada, M. Hayashi, K. Asano and T. Matuda. 1977. Studies on aculeacin. I: Isolation and characterization of aculeacin A. J. Antibiot. 30: 297–302.
Mori, H., S. Funayama, Y. Sudo, K. Komiyama and S. Ōmura. 1990. A new antibiotic, 13-hydroxyglucopiericidin A. Isolation, structure elucidation and biological characteristics. J. Antibiot. 43: 1329–1331.
Murao, S., T. Sakai, H. Gibo, T. Nakayama and T. Shin. 1991. An novel trehalase inhibitor, trehalostatin, produced byAmycolatopsis trehalostaticus. Agric. Biol. Chem. 55: 895–897.
Murata, M., H. Tanaka and S. Ōmura. 1987. 7-Hydro-8-methylpteroylglutamic acid, a new anti-folate from an actinomycete. Fermentation, isolation, structure and biological activity. J. Antibiot. 40: 251–257.
S.-Nakagawa, P., Y. Fukushi, K. Maebashi, N. Imamura, Y. Takahashi, Y. Tanaka, H. Tanaka and S. Ōmura. 1986. Izupeptins A and B, new glycopeptide antibiotics produced by an actinomycete. J. Antibiot. 39: 1719–1723.
Nakagawa, A., Y. Iwai, H. Shimizu and S. Ōmura. 1986. Enhanced antimicrobial activity of acetyl derivatives of cervinomycin. J. Antibiot. 39: 1636–1638.
Nakagawa, A., N. Fukamachi, K. Yamaki, M. Hayashi, S. Oh-ishi, B. Kobayashi and S. Ōmura. 1987. Inhibition of platelet aggregation by medermycin and its related isochromanequinone antibiotics. J. Antibiot. 40: 1075–1076.
Neuroth, A.R. and S.B.H. Kent. 1988. The pre-S region of hepadnavirus envelope proteins. Adv. Viral Res. 34: 65–142.
Nicolaou, K.C. and W.M. Dai. 1991. Chemistry and biology of the endiyne anticancer antibiotics. Angew. Chem. 30: 1387–1416.
Nishida, H., H. Tomoda, J. Cao, S. Araki, S. Okuda and S. Ōmura. 1991. Purpactins, new inhibitors of acyl-CoA: cholesterol acyl-transferase produced byPenicillium purpurogenum. III. Chemical modification of purpactin A. J. Antibiot. 44: 152–159.
Nishikawa, K., C. Shibasaki, M. Hiratsuka, M. Arakawa, K. Takahashi and T. Takeuchi. 1991. Antitumor spectrum of deoxyspergalin and its lack of cross-resistnace to other antitumor agents. J. Antibiot. 44: 1101–1109.
Ochi, K. 1989. Heterogeneity of ribosomal proteins amongStreptomyces species and its application to identification. J. Gen. Microbiol. 135: 2635–2642.
Oda, K., Y. Fukuda, S. Murao, K. Uchida and M. Kainosho. 1989. A novel proteinase inhibitor, tyrostatin, inhibiting some pepstatin-insensitive carboxyl proteinases. Agric. Biol. Chem. 53: 405–415.
Oikawa, T., K. Hirotani, M. Shimamura, H. Ashino-Fuse and T. Iwaguchi. 1989. Powerful antiangiogenic activity of herbimycin A (named angiostatic antibiotic). J. Antibiot. 42: 1202–1204.
Oki, T., O. Tenmyo, M. Hirano, K. Tomatsu and H. Kamei. 1990. Pradimicins A, B and C. New antifungal antibiotics. II. In vitro and in vivo biological activities. J. Antibiot. 43: 763–770.
Ōmura, S. 1986. Philosophy of new drug discovery. Microbiol. Rev. 50: 259–279.
Ōmura, S. 1988. Search for bioactive compounds from microorganisms-Strategy and methods. In: Biology of Actinomycetes-88 (Okami, Y., T. Beppu and H. Ogawara, eds.), pp. 26–32, Japanese Scientific Society Press, Tokyo.
Ōmura, S. and Y. Tanaka. 1991. Strategy and methods in screening of microbial metabolites for plant protection. In: Pesticide Chemistry (Frehse, H., ed.), pp. 87–96, VCH Publishers, Weinheim.
Ōmura, S., Y. Iwai, A. Hirano, A. Nakagawa, J. Awaya, H. Tsuchiya and Y. Tanahashi. 1977. A new alkaloid AM-2282 of streptomycete origin. Taxonomy, fermentation, isolation and preliminary characterization. J. Antibiot. 30: 275–282.
Ōmura, S., A. Nakagawa and N. Sadakane. 1979. Structure of herbimycin, a new ansamycin antibiotic. Tetrahedron Lett. 1979: 4223–4326.
Ōmura, S., Y. Iwai, Y. Takahashi, K. Kojima, K. Otoguro and R. Oiwa. 1981. Type of diaminopimelic acid different in aerial and vegetative mycelia of setamycin-producing actinomycete KM-6054. J. Antibiot. 34: 1633–1634.
Ōmura, S., K. Otoguro, T. Nishikiori, R. Oiwa and Y. Iwai. 1981. Setamycin, a new antibiotic. J. Antibiot. 34: 1253–1256.
Ōmura, S., H. Ikeda, F. Malpartida, H.M. Kieser and D.A. Hopwood. 1986. Production of new hybrid antibiotics, mederrhodins A and B by a genetically engineered strain. Antimicrob. Agents Chemother. 29: 13–19.
Ōmura, S., N. Imamura, K. Kawakita, Y. Mori, Y. Yamazaki, R. Masuma, Y. Takahashi, H. Tanaka, L.-Y. Huang and H.B. Woodruff. 1986. Ahpatinins, new acid protease inhibitors containing 4-amino-3-hydroxy-5-phenylpentanoic acid. J. Antibiot. 39: 1079–1085.
Ōmura, S., N. Imamura, R. Oiwa, H. Kuga, R. Iwata, R. Masuma and Y. Iwai. 1986. Clostomicins, new antibiotics produced byMicromonospora echinospora subsp.Armeniaca subsp. nov. I. Production, isolation, and physicochemical and biological properties. J. Antibiot. 39: 1407–1412.
Ōmura, S., A. Nakagawa, N. Fukamachi, K. Ogoturo and B. Kobayashi. 1986. Aggreceride, a new platelet aggregation inhibitor fromStreptomyces. J. Antibiot. 39: 1180–1181.
Ōmura, S., H. Tomoda, Q.-M. Xu, Y. Takahashi and Y. Iwai. 1986. Triacsins, new inhibitors of acyl-CoA synthetase produced byStreptomyces. J. Antibiot. 39: 1211–1218.
Ōmura, S. A. Nakagawa, N. Fukamachi, M. Miura, Y. Takahashi, K. Komiyama and B. Kobayashi. 1988. OM-4842, a new platelet aggregation inhibitor fromStreptomyces. J. Antibiot. 41: 812–813.
Ōmura, S., Y. Tanaka, K. Hisatome, S. Miura, Y. Takahashi, A. Nakagawa, H. Imai and H.B. Woodruff. 1988. Phthoramycin, a new antibiotic active against a plant pathogen,Phytophtora sp. J. Antibiot. 41: 1910–1912.
Ōmura, S., S. Eda, S. Funayama, Y. Takahashi, K. Komiyama and H.B. Woodruff. 1989. Studies on a novel antitumor antibiotic, phenazinomycin: Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics. J. Antibiot. 42: 1037–1042.
Ōmura, S., Y. Tanaka, K. Kanaya, M. Shinose and Y. Takahashi. 1990. Phthoxazolin, a specific inhibitor of cellulose biosynthesis, produced by a strain ofStreptomyces sp. J. Antibiot. 43: 738–741.
Ōmura, S., T. Fujimoto, K. Otoguro, K. Matsuzaki, R. Moriguchi, H. Tanaka and Y. Sasaki. 1991. Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells. J. Antibiot. 44: 113–116.
Ōmura, S., H. Ikeda and H. Tanaka. 1991. Selective production of specific components of avermectins inStreptomyces avermitilis. J. Antibiot. 44: 560–563.
Ōmura, S., Y. Kondo and Z. Itoh. 1990. Motilide, motilinlike macrolide. In: Motilin (Itoh, Z., ed.), pp. 245–256, Academic Press, New York.
Ōmura, S., K. Matsuzaki, T. Fujimoto, K. Kosuge, T. Furuya, S. Fujita and A. Nakagawa. 1991. Structure of lactacystin, a new microbial metabolite which induces differentiation of neuroblastoma cells. J. Antibiot. 44: 117–118.
Osada H., H. Koshino, T. Kudo, R. Onose and K. Isono. 1992. A new inhibitor of protein kinase C, RK-1409 (7-oxostaurosporine). I. Taxonomy, and biological activity. J. Antibiot. 45: 189–194.
Parker, W.L., J. O'Sullivan and R.B. Sykes. 1986. Naturally occurring monobactams. Adv. Appl. Microbiol. 31: 181–205.
Peczynska-Czoch, W., M. Mordarski, L. Kaczmarek and P. Nanka-Namiriski. 1987. Microbial transformation of azacarbozoles. I. N-methylation of alpha-, beta-, and gammacarbolines byKitasatosporia setae strain. Arch. Immunol. Ther. Exp. 35: 89–95.
Perlman, D. and G.P. Peruzzotti. 1970. Microbial metabolites as potentially useful pharmacologically active agents. Adv. Appl. Microbiol. 12: 227–294.
Sakuda, S., Y. Nishimoto, M. Ohi, M. Watanabe, S. Takayama, A. Isogai and Y. Yamada. 1990. Effect of demethylallosamidin, a potent yeast chitinase inhibitor, on the cell division of yeast. Agric. Biol. Chem. 54: 1333–1335.
Sasaki, Y., M. Seto, K. Komatu and S. Ōmura. 1991. Staurosporine, a protein kinase inhibitor, attenuates intracellular calcium ion-dependent contractions of strips of rabbit aorta. Eur. J. Pharmacol. 202: 367–372.
Satoh, T., N. Inotomi, H. Satoh, S. Marui, Z. Itoh and S. Ōmura. 1990. EM-523, an erythromycin derivative, and motilin show similar contractile activity in isolated rabbit intestine. J. Pharmacol. Exp. Ther. 254: 940–944.
Sawada, H., M. Motoike, S. Kudo, T. Watanabe and A Kuroda. 1989. Manufacture of phospholipase D withKitasatosporia SK-60. Japan Kokai Tokyo Koho JP 01-80, 285.
Schulman, M.D., D. Valentino, S. Streicher and C. Ruby. 1987.Streptomyces avermitilis' mutants defective in methylation of avermectins. Antimicrob. Agents Chemother. 31: 744–747.
Schwartz, J.P. and E. Costa. 1978. Regulation of nerve growth-factor content in a neuroblastoma cell line. Neuroscience 3: 473–480.
Serizawa, N., K. Nakagawa, K. Hamano, Y. Tsujita, A. Terahara and H. Kuwano. 1983. Microbial hydroxylation of ML-236B (compactin) and monacolin K (MB-530B). J. Antibiot. 36: 604–607.
Shibata, K., S. Satsumabayashi, A. Nakagawa and S. Ōmura. 1986. The structure and cytocidal activity of herbimycin C. J. Antibiot. 39: 1630–1633.
Smith III, A.B., J.L. Wood, W. Wong, A.E. Gould, C.J. Rizzo, S. Funayama and S. Ōmura. 1990. (+)-Trienomycins A, B, and C: Relative and absolute stereochemistry. J. Am. Chem. Soc. 112: 7425–7426.
Taguchi, R., H. Sugawara, Y. Miyazaki, T. Mizuno, M. Nomura, M. Sugiyama, H. Saito, G. Yabuta and A. Furuichi. 1989. Agrochemical F-0368 manufacture withKitasatosporia. Japan Kokai Tokyo koho JP 01-231, 892.
Takahashi, Y. 1989. Discovery and taxonimic studies of the genusKitasatosporia. Actinomycetologica (Tokyo) 3: 55–62 (in Japanese).
Takahashi, Y. and S. Ōmura. 1987.Kitasatosporia, a genus of the order Actinomycetales. Kitasato Arch. Exp. Med. 60: 1–14.
Takahashi, Y., Y. Iwai and S. Ōmura. 1983. Relationship between cell morphology and the types of diaminopimelic acid inKitasatosporia setae. J. Gen. Appl. Microbiol. 29: 459–465.
Takahashi, Y., Y. Iwai, H. Tomoda, R. Nimura, T. Kinoshita and S. Ōmura. 1989. Optical resolution of 2,6-diaminopimelic acid stereoisomers by high performance liquid chromatography for the chemotaxomy of actinomycete strains. J. Gen. Appl. Microbiol. 35: 27–32.
Takahashi, Y., Y. Iwai and S. Ōmura. 1991. Mode of submerged spore formation inKitasatosporia setae. J. Gen. Appl. Microbiol. 37: 261–266.
Takahashi, Y., Y. Seki, Y. Iwai and S. Ōmura. 1991. Taxomic properties of fiveKitasatosporia strains isolated by a new method. Kitasato Arch. Exp. Med. 64: 123–132.
Takeshima, H., J. Inokoshi, Y. Takada, H. Tanaka and S. Ōmura. 1989. A deacylation enzyme for aculeacin A, a neutral lipopeptide antibiotic fromActinoplanes utahensis: purification and characterization. J. Biochem. 105: 606–610.
Takeuchi, T., T. Hara, H. Naganawa, M. Okada, M. Hamada, H. Umezawa, S. Gomi, M. Sezaki and S. Kondo. 1988. New antifungal antibiotics, benanomicins A and B from an Actinomycete. J. Antibiot. 41: 807–811.
Tamamura, T., T. Sawa, K. Isshiki, T. Masuda, Y. Homma, H. Iinuma, H. Naganawa, M. Hamada, T. Takeuchi and H. Umezawa. 1985. Isolation and characterization of terpentecin, a new antitumor antibiotic. J. Antibiot. 38: 1664–1669.
Tamaoki, T. 1991. Use and specificity of staurosporine UCN-01, and calphostin C as protein kinase inhibitors. In: Methods in Enzymology, Vol. 201. Protein Phosphorylation Part B (Hunter, T. and B.M. Sefton, eds.), pp. 340–347, Academic Press, San Diego.
Tamaoki, T. and H. Nakano. 1990. Potent and specific inhibitors of protein kinase C of microbial origin. Biol./ Technology 8: 732–733.
Tanaka, H. and S. Ōmura. 1989. New adenosine deaminase inhibitors, adechlorin and adecypenol. In: Novel Microbial Products for Medicine and Agriculture (Demain, A.L., G.A. Somkuti, J.C. Hunter-Cevera and H.W. Rossmoore, eds.), pp. 67–72. Elsevier, Amsterdam.
Tanaka, Y., K. Hirata, Y. Takahashi, Y. Iwai and S. Ōmura. 1987. Globopeptin, a new antifungal peptide antibiotic. J. Antibiot. 40: 242–244.
Tomoda, H. and S. Ōmura. 1990. New strategy for discovery of enzyme inhibitors: Screening with intact mammalian cells or intact microorganisms having special functions. J. Antibiot. 42: 1207–1222.
Tomoda, H., R. Iwata, Y. Takahashi, Y. Iwai, R. Oiwa and S. Ōmura. 1986. Lustromycin, a new antibiotic produced byStreptomyces sp. J. Antibiot. 39: 1205–1210.
Tomoda, H., K. Igarashi and S. Ōmura. 1987. Inhibition of acyl-CoA synthetase by triacsins. Biochim. Biophys. Acta 921: 595–598.
Tomoda, H., H. Kumagai, H. Tanaka and S. Ōmura. 1987. F-244 specifically inhibits 3-hydroxy-3-methyl-glutarylcoenzyme A synthase. Biochim. Biophys. Acta 922: 351–356.
Tomoda, H., H. Kumagai, Y. Tanaka, Y. Iwai and S. Ōmura. 1988. F-244 (1233A), a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A synthase: Taxonomy of producing strain, fermentation, isolation and biological properties. J. Antibiot. 41: 247–249.
Tomoda, H., K. Igarashi, J.C. Cyong and S. Ōmura. 1987. Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation. J. Biol. Chem. 266: 4214–4219.
Tomoda, H., H. Nishida, R. Masuma, C. Cao, S. Okuda and S. Ōmura. 1991. Purpactins, new inhibitors of acyl-CoA: cholesterol acyltransferase produced byPenicillium purpurogenum. I. Production, isolation and physico-chemical and biological properties. J. Antibiot. 44: 136–143.
Traxler, P., W. Kump, K. Mueller and W. Tosch. 1990. Hypolipidemic activity of rifamycin derivatives. J. Med. Chem. 33: 552–560.
Uehara, Y., M. Hori, T. Takeuchi and H. Umezawa. 1985. Screening of agents which convert ‘transformed morphology’ of Rous sarcoma virus-infected rat kidney cells to ‘normal morphology’: Identification of an active agent as herbimycin and its inhibition of intracellularsrc kinase. Jpn. J. Cancer Res. (Gann) 76: 672–675.
Uehara, Y., Y. Murakami, Y. Sugimoto and S. Mizuno. 1989. Mechanism of reversion of Rous sarcoma virus transformation by herbimycin A: Reduction of total phosphotyrosine levels due to reduced kinase activity and increased turnover of p60v-src. Cancer Res. 49: 780–785.
Umezawa, I., K. Komiyama, H. Oka, K. Okada, S. Tomisaka, T. Miyano and S. Takano. 1984. A new antitumor antibiotic, kazusamycin. J. Antibiot. 37: 706–711.
Umezawa, K. and M. Imoto. 1991. Use of erbstatin as protein-tyrosine kinase inhibitor. In: Methods in Enzymology Vol. 201. Protein phosphorylation Part B (Hunter, T. and B.M. Sefton, eds.), pp. 379–385, Academic Press, San Diego.
Wakisaka, Y., Y. Kawamura, Y. Sasuda, K. Koizumi and Y. Nishimoto. 1982. A selective isolation procedure forMicromonospora. J. Antibiot. 35: 822–836.
Weber, J.M., J.O. Leung, S.J. Swanson, K.B. Idler and J.B. McAlpine. 1991. An erythromycin derivative produced by targeted gene disruption inSaccharopolyspora erythreae. Science 252: 114–117.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Omura, S. Trends in the search for bioactive microbial metabolites. Journal of Industrial Microbiology 10, 135–156 (1992). https://doi.org/10.1007/BF01569759
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01569759