Abstract
The genetic basis for the biosynthesis of large polypeptide antibiotics such as nisin has not been explained so far. We show here that the structural gene epiA encoding the antibiotic epidermin1,2 from Staphylococcus epidermidis is located on a 54-kilobase plas-mid and codes for a 52-amino-acid prepeptide, which is processed to the tetracyclic 21-peptide amide antibiotic. The mature sequence of epidermin corresponds to the C-terminal 22-peptide segment of pre-epidermin and contains the precursor amino acids Ser, Thr and Cys, from which the unusual amino-acid constituents are derived. The more lipophilic epidermin is cleaved at a hydrophilic turn between Arg–1 and Ile+1 from the N-terminal segment –30 to –1, which probably assumes a partially amphiphilic a-helix conformation. We propose that the N-terminus (–30 to –1) plays a cooperative role during modification reactions and prevents toxicity of the mature epidermin to the producing strain before the antibiotic is cleaved off and secreted.
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References
Allgaier, H., Jung, G., Werner, R. G., Schneider, U. & Zähner, H. Angew. Chem. 24, 1051–1053 (1985).
Allgaier, H., Jung, G., Werner, R. G., Schneider, U. & Zähner, H. Eur. J. Biochem. 160, 9–22 (1986).
Gross, E. & Morell, J. L. J. Am. chem. Soc. 93, 4634–4635 (1971).
Gross, E., Klitz, H. & Craig, L. C. Hoppe-Seyler's Z. physiol. Chem. 354, 799–801 (1973).
Gross, E. Adv. exp. Med. Biol. 86b, 131–153 (1977).
Wakamiya, T., Ueki, Y., Shiba, T., Kido, Y. & Motoki, Y. Tetrahedron Lett. 26, 665–668 (1985).
Kessler, H., Steuernagel, S., Gillessen, D. & Kamiyama, T. Helv. chim. Acta 70, 726–741 (1987).
Sahl, H.-G. J. Bact. 162, 833–836 (1985).
Novick, R. P. & Bouanchaud, D. Ann. N. Y. Acad. Sci. 182, 279–294 (1971).
Southern, E. J. molec. Biol 98, 503–517 (1975).
Heinrich, P., Rosenstein, R., Böhmer, M., Sonner, P. & Götz, F. Molec. gen. Genet. 209, 563–569 (1987).
Hruby, V. J. & Smith, C. W. in The Peptides, Analysis, Synthesis, Biology Vol. 8 (eds. Udenfriend, S. & Meienhofer, J.) 77–197 (Academic, Orlando, Florida, 1987).
Fukase, K. et al. in Peptide Chemistry 1987 (eds Shiba, T. & Sakakibara, S.) 337–342 (Protein Research Foundation, Osaka, 1988).
Sanger, F., Coulson, A. R., Barell, B. G., Smith, A. J. & Roe, B. A. J. molec. Biol. 143, 161–178 (1980).
Hattori, T. A. & Sakaki, Y. Analyt. Biochem. 152, 232–238 (1984).
Karplus, P. A. & Schulz, G. E. Naturwissenschaften 72, 212–213 (1985).
Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).
Hopp, T. P. & Woods, K. R. Molec. Immun. 20, 483–489 (1983).
Garnier, J., Osguthorpe, D. J. & Robson, B. J. molec. Biol. 120, 97–120 (1978).
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Schnell, N., Entian, KD., Schneider, U. et al. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature 333, 276–278 (1988). https://doi.org/10.1038/333276a0
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DOI: https://doi.org/10.1038/333276a0
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