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Colutellin A, an immunosuppressive peptide from Colletotrichum dematium

¹ Department of Plant Sciences, Montana State University, Bozeman, MT 59717, USA
² Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA
³ Departments of Immunobiology and Molecular Biophysics & Biochemistry, Yale University School of Medicine, S625A, The Anlyan Center (TAC), 300 Cedar Street, New Haven, CT 06520, USA
⁴ Department of Neurology, David Geffen School of Medicine and Molecular Biology Institute and Brain Research institute, University of California, Los Angeles, CA 90095, USA
⁵ Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA
⁶ Department of Plant and Animal Biology, Brigham Young University, Provo, UT 94602, USA
⁷ Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA

Correspondence
Gary Strobel
uplgs{at}montana.edu

Colletotrichum dematium is an endophytic fungus recovered from a Pteromischum sp. growing in a tropical forest in Costa Rica. This fungus makes a novel peptide antimycotic, colutellin A, with a MIC of 3.6 µg ml^–1 (48 h) against Botrytis cinerea and Sclerotinia sclerotiorum. Collutellin A has a mass of 1127.7 Da and contains residues of Ile, Val, Ser, N-methyl-Val and β-aminoisobutryic acid in nominal molar ratios of 3 : 2 : 1 : 1 : 1, respectively. Independent lines of evidence suggest that the peptide is cyclic and sequences of Val-Ile-Ser-Ile and Ile-Pro-Val have been deduced by MS/MS as well as Edman degradation methods. Colutellin A inhibited CD4⁺ T-cell activation of interleukin 2 (IL-2) production with an IC₅₀ of 167.3±0.38 nM, whereas cyclosporin A in the same test yielded a value of 61.8 nM. Inhibition of IL-2 production by collutellin A at such a low concentration indicates the potential immunosuppressive activity of this compound. In repeated experiments, cyclosporin A at or above 8 µg ml^–1 exhibited high levels of cytotoxicity on human peripheral blood mononuclear cells, whereas collutellin A or DMSO (carrier) alone, after 24 and 48 h of culture, exhibited no toxicity. Because of these properties collutellin A has potential as a novel immunosuppressive drug.

The GenBank/EMBL/DDBJ accession number for the rDNA sequences of C. dematium CR-12 is EU330193.