Abstract
A strain of Acremonium luzulae (Fuckel) W. Gams was selected in screening new microorganisms for biological control of fruit postharvest diseases, especially gray and blue mold diseases on apples and strawberries. This strain manifests a very strong activity against a large number of phytopathogenic fungi. In this work, the product responsible for this antifungal activity was isolated from modified Sabouraud dextrose broth cultures of A. luzulae. It was purified to homogeneity by reverse-phase column chromatography. On the basis of UV, infrared, and 1H and 13C nuclear magnetic resonance spectra, mass spectral analysis, and the amino acid composition of the acid hydrolysates, the antibiotic was determined to be cyclosporin C. Cyclosporin C showed a broad-spectrum activity against filamentous phytopathogenic fungi but no activity against bacteria or yeasts. Its antifungal activity is only fungistatic. In contrast to Tolypocladium inflatum, another cyclosporin-producing strain, A. luzulae, did not produce additional cyclosporins. This was confirmed by in vivo-directed biosynthesis.
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Selected References
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- Bach J. F. Cyclosporine in autoimmune diseases. Transplant Proc. 1989 Jun;21(3 Suppl 1):97–113. [PubMed] [Google Scholar]
- Billich A., Zocher R. Enzymatic synthesis of cyclosporin A. J Biol Chem. 1987 Dec 25;262(36):17258–17259. [PubMed] [Google Scholar]
- Borel J. F. Ciclosporin and its future. Prog Allergy. 1986;38:9–18. [PubMed] [Google Scholar]
- Borel J. F., Feurer C., Gubler H. U., Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976 Jul;6(4):468–475. doi: 10.1007/BF01973261. [DOI] [PubMed] [Google Scholar]
- Borel J. F. Pharmacology of cyclosporine (sandimmune). IV. Pharmacological properties in vivo. Pharmacol Rev. 1990 Sep;41(3):259–371. [PubMed] [Google Scholar]
- Bram R. J., Hung D. T., Martin P. K., Schreiber S. L., Crabtree G. R. Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location. Mol Cell Biol. 1993 Aug;13(8):4760–4769. doi: 10.1128/mcb.13.8.4760. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cagnoli-Bellavita N., Ceccherelli P., Mariani R., Polonsky J., Baskevitch Z. Structure du virescenoside C, nouveau métabolite de Oospora virescens (Link) Wallr. Eur J Biochem. 1970 Aug;15(2):356–359. doi: 10.1111/j.1432-1033.1970.tb01015.x. [DOI] [PubMed] [Google Scholar]
- Fischer G., Wittmann-Liebold B., Lang K., Kiefhaber T., Schmid F. X. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature. 1989 Feb 2;337(6206):476–478. doi: 10.1038/337476a0. [DOI] [PubMed] [Google Scholar]
- Gurusiddaiah S., Winward L. D., Burger D., Graham S. O. Pantomycin: a new antimicrobial antibiotic. Mycologia. 1979 Jan-Feb;71(1):103–118. [PubMed] [Google Scholar]
- Heitman J., Movva N. R., Hall M. N. Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression. New Biol. 1992 May;4(5):448–460. [PubMed] [Google Scholar]
- Jacques P., Ongena M., Gwose I., Seinsche D., Schröder H., Delfosse P., Thonart P., Taraz K., Budzikiewicz H. Structure and characterization of isopyoverdin from Pseudomonas putida BTP1 and its relation to the biogenetic pathway leading to pyoverdins. Z Naturforsch C. 1995 Sep-Oct;50(9-10):622–629. doi: 10.1515/znc-1995-9-1005. [DOI] [PubMed] [Google Scholar]
- Kleinkauf H., von Döhren H. Nonribosomal biosynthesis of peptide antibiotics. Eur J Biochem. 1990 Aug 28;192(1):1–15. doi: 10.1111/j.1432-1033.1990.tb19188.x. [DOI] [PubMed] [Google Scholar]
- Lawen A., Traber R., Geyl D., Zocher R., Kleinkauf H. Cell-free biosynthesis of new cyclosporins. J Antibiot (Tokyo) 1989 Aug;42(8):1283–1289. doi: 10.7164/antibiotics.42.1283. [DOI] [PubMed] [Google Scholar]
- Lawen A., Zocher R. Cyclosporin synthetase. The most complex peptide synthesizing multienzyme polypeptide so far described. J Biol Chem. 1990 Jul 5;265(19):11355–11360. [PubMed] [Google Scholar]
- Maiorca R., Scolari F., Savoldi S., Sandrini S., Scaini P., Cristinelli L. Cyclosporin and renal injury. Adv Exp Med Biol. 1989;252:273–284. doi: 10.1007/978-1-4684-8953-8_26. [DOI] [PubMed] [Google Scholar]
- Myers B. D. Cyclosporine nephrotoxicity. Kidney Int. 1986 Dec;30(6):964–974. doi: 10.1038/ki.1986.280. [DOI] [PubMed] [Google Scholar]
- Razafindralambo H., Paquot M., Hbid C., Jacques P., Destain J., Thonart P. Purification of antifungal lipopeptides by reversed-phase high-performance liquid chromatography. J Chromatogr. 1993 Jun 4;639(1):81–85. doi: 10.1016/0021-9673(93)83091-6. [DOI] [PubMed] [Google Scholar]
- Sadeg N., Pham-Huy C., Martin C., Warnet J. M., Claude J. R. In vitro comparative study on nephrotoxicity of cyclosporine A, its metabolites M1, M17, M21, and its analogues cyclosporines C and D in suspensions of rabbit renal cortical cells. Drug Chem Toxicol. 1994;17(2):93–111. doi: 10.3109/01480549409014304. [DOI] [PubMed] [Google Scholar]
- Sadeg N., Pham-Huy C., Rucay P., Righenzi S., Halle-Pannenko O., Claude J. R., Bismuth H., Duc H. T. In vitro and in vivo comparative studies on immunosuppressive properties of cyclosporines A, C, D and metabolites M1, M17 and M21. Immunopharmacol Immunotoxicol. 1993 Mar-Jun;15(2-3):163–177. doi: 10.3109/08923979309025992. [DOI] [PubMed] [Google Scholar]
- Schmidt B., Riesner D., Lawen A., Kleinkauf H. Cyclosporin synthetase is a 1.4 MDa multienzyme polypeptide. Re-evaluation of the molecular mass of various peptide synthetases. FEBS Lett. 1992 Aug 3;307(3):355–360. doi: 10.1016/0014-5793(92)80712-p. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Hayano T., Suzuki M. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature. 1989 Feb 2;337(6206):473–475. doi: 10.1038/337473a0. [DOI] [PubMed] [Google Scholar]
- Traber R., Hofmann H., Kobel H. Cyclosporins--new analogues by precursor directed biosynthesis. J Antibiot (Tokyo) 1989 Apr;42(4):591–597. doi: 10.7164/antibiotics.42.591. [DOI] [PubMed] [Google Scholar]
- Traber R., Kuhn M., Rüegger A., Lichti H., Loosli R. H., von Wartburg A. Die Struktur von Cyclosporin C. Helv Chim Acta. 1977 Jun 1;60(4):1247–1255. doi: 10.1002/hlca.19770600414. [DOI] [PubMed] [Google Scholar]
- Weber G., Schörgendorfer K., Schneider-Scherzer E., Leitner E. The peptide synthetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame. Curr Genet. 1994 Aug;26(2):120–125. doi: 10.1007/BF00313798. [DOI] [PubMed] [Google Scholar]
- von Wartburg A., Traber R. Chemistry of the natural cyclosporin metabolites. Prog Allergy. 1986;38:28–45. [PubMed] [Google Scholar]