Abstract
In search for new zaragozic acids and their derivatives that are potent inhibitors of squalene synthase, discomycetes of the order Leotiales were cultured and their fermentation broth was assayed. Three strains in 2 unidentified species ofMollisia were found to produce zaragozic acid D3 and three new analogs (F-10863s). Fermentative production, productivity of F-10863s and mycological characteristics of the producers are described. Discomycetes are expected to be a biological resource providing novel bioactive compounds.
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Literature cited
Ainsworth, G. C. 1973. Introduction and keys to higher taxa. In: The fungi, vol. IV A, (ed. by Ainsworth, G. C., Sparrow, F. K. and Sussman, A. S.), pp. 1–7. Academic Press, New York.
Berbee, M. L. 1996. Loculoascomycete origins and evolution of filamentous ascomycete morphology based on 18S rRNA gene sequence data. Mol. Biol. Evol.13: 462–470.
Bergstrom, J. D., Dufresne, C., Bills, G. F., Nallin-Omstead, M. and Byrne, K. 1995. Discovery, biosynthesis, and mechanism of action of the zaragozic acids: Potent inhibitors of squalene synthase. Ann. Rev. Microbiol.49: 607–639.
Bergstrom, J. D., Kurtz, M. M., Rew, D. J., Amend, A. M., Karkas, J. D., Bostedor, R. G., Bansal, V. S., Dufresne, C., Van-Middlesworth, F. L., Hensens, O. D., Liesch, J. M., Zink, D. L., Wilson, K. E., Onishi, J., Milligan, J. A., Bills, G., Kaplan, L., Nallin-Omstead, M., Jenkins, R. G., Huang, L., Meinz, M. S., Quinn, L., Burg, R. W., Kong, Y. L., Mochales, S., Mojena, M., Martin, I., Pelaez, F., Diez, M. T. and Alberts, A. W. 1993. Zaragozic acids: A family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. Proc. Natl. Acad. Sci. USA90: 80–84.
Bills, G. F. 1995. Analyses of microfungal diversity from a user's perspective. Can. J. Bot.73 (Suppl. 1): S33–41.
Bills, G. F., Peláez, F., Polishook, J. D., Diez-Matas, M. T., Harris, G. H., Clapp, W. H., Dufresne, C., Byrne, K. M., Nallin-Omstead, M., Jenkins, R. G., Mojena, M., Huang, L. and Bergstrom, J. D. 1994. Distribution of zaragozic acids (squalestatins) among filamentous ascomycetes. Mycol. Res.98: 733–739.
Dawson, M. J., Farthing, J. E., Marshall, P. S., Middleton, R. F., O'Neill, M. J., Shuttleworth, A., Stylli, C., Tait, R. M., Taylor, P. M., Wildman, H. G., Buss, A. D., Langley, D. and Hayes, M. V. 1992. The squalestatins, novel inhibitors of squalene synthase produced by a species ofPhoma. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity. J. Antibiotics45: 639–647.
Hasumi, K., Tachikawa, K., Sakai, K., Murakawa, S., Yoshikawa, N., Kumazawa S. and Endo, A. 1993. Competitive inhibition of squalene synthetase by squalestatin 1. J. Antibiotics46: 689–691.
Hawksworth, D. L., Kirk, P. M., Sutton, B. C. and Pegler, D. N. 1996. Dictionary of the fungi, 8th ed., C.A.B. International, Wallingford.
Hosoya, T. and Otani, Y. 1997. Hyaloscyphaceae in Japan (1): Non-glassy-haired members of the tribe Hyaloscypheae. Mycoscience38: 171–186.
Korf, R. P. 1973. Discomycetes and Tuberales. In: The fungi, vol. IV A, (ed. by Ainsworth, G. C., Sparrow, F. K. and Sussman, A. S.), pp. 249–319. Academic Press, New York.
Kornerup, A. and Wanscher, J. H. 1978. Methuen handbook of colour, 3rd ed. Eyre Methuen, London.
Le Gal, M. and Mangenot, F. 1958. Contribution a l'etude des Mollisioidees. II. Rev. Mycol. Fr.23: 28–86.
Nakanishi, S., Ando, K., Kawamoto, I., Yasuzawa, T., Sano, H. and Kase, H. 1989. KS-504 compounds, novel inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase fromMollisia ventosa. J. Antibiotics42: 1775–1783.
Otani, Y. 1989. List of discomycetes fungi recorded from Japan. Sci. Rept. Yokosuka City Mus.37: 61–81.
Rossman, A. 1996. A strategy for an all-taxa inventory of fungal biodiversity. In: Biodiversity and terrestrial ecosystems, (ed. by Peng, C. I. and Chou, C. H.), pp. 169–194. Inst. Botany, Acad. Sinica Monograph Series No. 14.
Schulz, B., Sucker, J., Aust, H. J., Krohn, K., Ludewig, K., Jones, P. G. and Döring, D. 1995. Biologically active secondary metabolites of endophyticPezicula species. Mycol. Res.99: 1007–1015.
Tanimoto, T., Hamano, K., Onodera, K., Hosoya, T., Kakusaka, M., Hirayama, T., Shimada, Y., Koga, T. and Tsujita, Y.. 1997. Biological activities of novel zaragozic acids, the potent inhibitors of squalene synthase produced by the fungus,Mollisia sp. SANK 10294. J. Antibiotics50: 390–394.
Tanimoto, T., Onodera, K., Hosoya, T., Takamatsu, Y., Kinoshita, T., Tago, K., Kogen, H., Fujioka, T., Hamano, K. and Tsujita, Y. 1996. Schizostatin, a novel squalene synthase inhibitor produced by the mushroom,Schizophyllum commune. I. Taxonomy, fermentation, isolation, physicochemical properties and biological activities. J. Antibiotics49: 617–623.
Tait, R. M. 1992. Development of a radiometric spot-wash assay for squalene synthase. Anal. Biochem.203: 310–316.
van der Kerk, G. J. M. and Overeem, J. C. 1957. Mollisin, a dichloronaphthoquinone derivative produced by the fungusMollisia caesia. Rec. Trav. Chim.76: 425–436.
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Hosoya, T., Tanimoto, T., Onodera, K. et al. Zaragozic acids production from discomycetes. Mycoscience 38, 305–311 (1997). https://doi.org/10.1007/BF02464088
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DOI: https://doi.org/10.1007/BF02464088