Summary
Streptomyces tendae Tü 901 produces the nucleoside peptide antibiotic nikkomycin. In shot-gun cloning experiments using pIJ699 as vector we isolated a 9.4-kb DNA fragment fromS. tendae which complemented the nikkomycin nonproducing mutant NP9 to the formation of nikkomycin C/Cx and Kx. Nikkomycins were identified by HPLC analyses and their characteristic UV spectra. In Southern hybridization experiments the cloned DNA exclusively reacted withS. tendae DNA sequences. As shown by Northern dot blotting, transcripts of the isolated DNA fragment were only detected during stationary growth and correlated with the extent of nikkomycin production. When the recombinant plasmid pNP113 containing the 9.4-kb DNA fragment was transferred into the over-producing mutant Tü901/ S2566, transformants exhibited a significantly decreased capacity for forming nikkomycin. Southern analysis of genomic DNA of these transformants revealed that severe rearrangements occurred in DNA sequences homologous to the 9.4-kb insert of pNP113.
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References
Binnie C, Warren M, Butler MJ (1989) Cloning and heterologous expression inStreptoinrces lividans ofStreptomyces rimosus genes involved in oxytetracycline biosynthesis. J Bacteriol 171:887–895
Bormann C, Huhn W, Zähner H, Rathmann R, Hahn H, König WA (1985) Metabolic products of microorganism 228. New nikkomycins produced by mutants ofStreptomyces tendae. J Antibiot 38:9–16
Bormann C, Mattern S, Schrempf H, Fiedler HP, Zähner H (1989) Isolation ofStreptomyces tendae mutants with an altered nikkomycin spectrum. J Antibiot 42:913–918
Butler MJ, Friend EJ, Hunter IS, Kaczmarek FS, Sugden DA, Warren M (1989) Molecular cloning of resistance genes and architecture of a linked gene cluster involved in biosynthesis of oxytetracycline byStreptomyces rimosus. MMG 215:231–238
Chater KF, Bruton CJ (1985) Resistance, regulatory and production genes for the antibiotic methylenomycin are clustered. EMBO J 4:1893–1897
Crueger W, Frommer W, Goelker C, Kaiser JW, Moeschler HF, Salcher O, Schedel M, Wehlmann H (1985) Neue Pflanzenwirkstoffe aus Mikroorganismen. Ausarbeitung von Herstellungsverfahren für Nikkomycine. Pflanzenschutznachr Bayer 38:305–348
Dähn U, Hagenmaier H, Höhne H, König WA, Wolf G, Zähner (1976) Nikkomycin, ein neuer Hemmstoff bei Pilzen. Arch Microbiol 107:143–160
Distler J, Braun C, Ebert A, Piepersberg W (1987) Gene cluster for streptomycin biosynthesis inStreptomyces griseus: analysis of a central region including the major resistance gene. MGG 208:204–210
Dyson P, Schrempf H (1987) Genetic instability and DNA amplification inStreptomvces lividans 66. J Bacteriol 169:4796–4803
Engel P (1987) Plasmid transformation ofStreptomyces tendae after heat attenuation of restriction. Appl Environ Microbiol 53:1–3
Fiedler HP (1984) Screening for new microbial products in biological fluids by ion-pair reversed-phase high performance liquid chromatography. J Chromatogr 316:487–494
Fiedler HP (1989) Nikkomycins and polyoxins. Natural products isolation. Seperation methodology of antimicrobials, antivirals and enzyme inhibitors. J Chromatogr Libr 43:153–189
Fiedler HP, Kurth R, Langhärig J, Delzer J, Zähner H (1982) Nikkomycins: microbial inhibitors of chitin synthetase. J Chem Technol Biotechnol 32:271–280
Fishman SE, Cox K, Larson JL, Reynolds PA, Seno ET, Yeh WK, Frank R van, Hershberger CL (1987) Cloning genes for the biosynthesis of a macrolide antibiotic. Proc Natl Acad Sci USA 84:8248–8252
Hopwood DA, Bibb MJ, Chater KF, Kieser T, Bruton CJ, Kieser HM, Lydiate DJ, Smith CP, Schrempf H (1985) Genetic manipulation ofStreptomyces — a laboratory manual. John Innes Foundation, Norwich, UK
Isono K, Suzuki S (1979) The polyoxins: pyrimidine nucleoside peptide antibiotics inhibiting fungal cell wall biosynthesis. Heterocycles 13:333–351
Isono K, Sato T, Hirasawa K, Funyama S, Suzuki S (1978) Biosynthesis of the nucleoside skeleton of the polyoxins. J Chem Soc 100:3937–3939
Kieser T (1984) Factors affecting the isolation of ccc DNA from Streptomyces lividans and Escherichia coli. Plasmid 12:19–36
Kieser T, Melton RE (1988) Plasmid pIJ699, a multicopy positive-selection vector forStreptomyces. Gene 65:83–91
Kurth R (1981) Untersuchungen zur Regulation der Nikkomycinbildung und Optimierung einer pO2-feeding-Fermenta-tion. Dissertation, University of Tübingen
Malpartida F, Hopwood DA (1984) Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. Nature 309:462–464
Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor
Motamedi H, Hutchinson CR (1987) Cloning and heterologous expression of a gene cluster for the biosynthesis of tetracenomycin C, the anthracycline antitumor antibiotic ofStreptomyces glaucescens. J Antibiot 36:1305–1311
Müller H, Furter R, Zähner H, Rast DM (1981) Effect of nikkomycin Z, nikkomycin X and polyoxin A on chitosomal chitin synthetase. Arch Microbiol 130:195–197
Murakami T, Anzai H, Imai S, Satoh A, Nagaoka K, Thompson CJ (1986) The bialaphos biosynthetic genes ofStreptomyces hygroscopicus: molecular cloning and characterization of the gene cluster. MGG 205:42–50
Ohnuki T, Imanaka T, Aiba S (1985) Self cloning inStreptomyces griseus of astr gene cluster for streptomycin biosynthesis and streptomycin resistance. J Bacteriol 164:85–94
Pigac J, Hranueli D, Smokvina T, Alacevic M (1982) Optimal cultural and physiological conditions for handling Streptomyces rimosus protoplasts. Appl Environ Microbiol 44:1178–1186
Schmidt RM, Pape H (1985) Biosynthesis of 4-formyl-4-imidazoline-2-one, the heterocyclic base of nikkomycin X. Z Naturforsch 41c:135–140
Shirahama T, Furumai T, Okanishi M (1981) A modified regeneration method for Streptomyces protoplasts. Agric Biol Chem 45:1271–1273
Sommer U (1983) Untersuchung zur Biosynthese von Nikkomycin D. Dissertation, University of Münster
Stanzak R, Matsushima P, Baltz RH, Rao RN (1986) Cloning and expression inStreptomyces lividans of clustered erythromycin biosynthesis genes from Streptomyces erythreus. Biotechnology 4:229–232
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Bormann, C., Aberle, K., Fiedler, HP. et al. Genetic complementation ofStreptomyces tendae deficient in nikkomycin production. Appl Microbiol Biotechnol 32, 424–430 (1990). https://doi.org/10.1007/BF00903777
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DOI: https://doi.org/10.1007/BF00903777