Abstract
The first insight into celesticetin biosynthetic gene cluster ofS. caelestis is presented. The genomic DNA of producing strain was digested, digoxigenin-labeled and hybridized with a set of probes designed according toS. lincolnensis gene sequences. Genes with high homology to the lincomycin biosynthetic genes coding for the predicted common parts of the pathway were identified inS. caelestis. Then, genomic DNA ofS. caelestis treated by a multiple digestion was hybridized with five digoxigenin-labeled probes to construct a rough restriction map. Two consecutive islands formed by the genes with a putative function in biosynthesis of the shared saccharide moiety revealed an organization similar to the lincomycin biosynthetic gene cluster. The celesticetin cluster was mapped and essential information was obtained for subsequent steps,i.e. isolation and sequence analysis of the cluster.
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Abbreviations
- CBC:
-
celesticetin biosynthetic cluster
- ccb :
-
celesticetin biosynthesis gene
- Cel:
-
celesticetin
- Dig:
-
digoxigenin
- chDNA:
-
chromosomal DNA
- LBC:
-
lincomycin biosynthetic cluster
- Lin:
-
lincomycin
- lmb :
-
lincomycin biosynthesis gene(s)
- lmr :
-
lincomycin resistance gene(s)
- Mtl:
-
methylthiolincosamide
- ORF:
-
open reading frame
- PCR(s):
-
polymerase chain reaction(s)
- Ppl:
-
4-propyl-l-proline
- S.cae. :
-
Streptomyces caelestis
- S.coe. :
-
Streptomyces coelicolor
- S.lin. :
-
Streptomyces lincolnensis
References
Ahlert J., Shepard E., Lomovskaya N., Zazopoulos E., Staffa A., Bachmann B.O., Huang K., Fonstein L.: The calicheamicin gene cluster and its iterative type I enediyne PKS.Science 297, 1173–1176 (2002).
Allali N., Afif H., Couturier M., Van Melderen L.: The highly conserved TldD and TldE proteins ofEscherichia coli are involved in microcin B17 processing and in CcdA degradation.J.Bacteriol. 184, 3224–3231 (2002).
Bentley S.D., Chater K.F., Cerdeno-Tarraga A.M., Challis G.L., Thomson N.R., James K.D., Harris D.E., Quail M.A., Kieser H., Harper D., Bateman A., Brown S., Chandra G., Chen C.W., Collins M., Cronin A., Fraser A., Goble A., Hidalgo J., Hornsby T., Howarth S., Huang C.H., Kieser T., Larke L., Murphy L., Oliver K., O’Neil S., Rabbinowitsch E., Rajandream M.A., Rutherford K., Rutter S., Seeger K., Saunders D., Sharp S., Squares R., Squares S., Taylor K., Warren T., Wietzorrek A., Woodward J., Barrell B.G., Parkhill J., Hopwood D.A.: Complete genome sequence of the model actinomyceteStreptomyces coelicolor A3(2).Nature 417, 141–147 (2002).
Brahme N.M., Gonzalez J.E., Rolls J.P., Hessler E.J., Mizsak S., Hurley L.H.: Biosynthesis of the lincomycins. 1. Studies using stable isotopes on the biosynthesis of the propyl- and ethyl-l-hygric acid moieties of lincomycins A and B.J.Am.Chem.Soc. 106, 7873–7878 (1984).
Calcutt M.J., Cundliffe E.: Cloning of a lincosamide resistance determinant fromStreptomyces caelestis, the producer of celesticetin, and characterization of the resistance mechanism.J.Bacteriol. 172, 4710–4714 (1990).
Chung S.-T., Manis J.J., McWethy S.J., Patt T.E., Witz D.F., Wolf H.J., Wovcha M.G.: Fermentation, biosynthesis, and molecular genetics of lincomycin, pp. 165–186 in W.R. Strohl (Ed.):Biotechnology of Industrial Antibiotics. Dekker, New York 1997.
Eustaquio A.S., Luft T., Wang Z.X., Gust B., Chater K.F., Li S.-M., Heide L.: Novobiocin biosynthesis: inactivation of the putative regulatory genenovE and heterologous expression of genes involved in aminocoumarin ring formation.Arch.Microbiol. 180, 25–32 (2003).
Hu Y., Phelan V., Ntai I., Farnet C.M., Zazopoulos E., Bachmann B.O.: Benzodiazepine biosynthesis inStreptomyces refuineus.Chem.Biol. 14, 691–701 (2007).
Janata J., Najmanová L., Novotná J., Holá K., Felsberg J., Spížek J.: PutativelmbI andlmbH genes form a singlelmbIH ORF inStreptomyces lincolnensis type strain ATCC 25466.Antonie van Leeuwenhoek 79, 277–284 (2001).
Kieser T., Bibb M.J., Bittner M.J., Chater K.F., Hopwood D.A.:Practical Streptomyces Genetics. John Innes Centre, Colney (Norwich) 2000.
Neusser D., Schmidt H., Spížek J., Novotná J., Peschke U., Kázchabeck S., Tichý P., Pipersberg W.: The geneslmbB1 andlmbB2 ofStreptomyces lincolnensis encode enzymes involved in the conversion ofl-tyrosine to propylproline during the biosynthesis of the antibiotic lincomycin A.Arch.Microbiol. 169, 322–332 (1998).
Novotná J., Honzátko A., Bednář P., Kopecký J., Janata J., Spížek J.:l-3,4-Dihydroxyphenylalanine-extradiol cleavage is followed by intramolecular cyclization in lincomycin biosynthesis.Eur.J.Biochem. 271, 3678–3683 (2004).
Novotná J., Olšovská J., Honzátko A., Bednář P., Novák P., Kopecký J., Janata J., Spížek J.: The initial steps in the lincomycin biosynthesis.Acta Microbiol.Immunol.Hung. 52 (Suppl.), 113 (2005).
Peschke U., Schmidt H., Zhang H.-Z., Piepersberg W.: Molecular characterization of the lincomycin-production gene cluster ofStreptomyces lincolnensis 78-11.Mol.Microbiol. 16, 1137–1156 (1995).
Pojer F., Li S.-M., Heide L.: Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics.Microbiology 148, 3901–3911 (2002).
Steffensky M., Mühlenweg A., Wang Z.X., Li S.-M., Heide L.: Identification of the novobiocin biosynthetic gene cluster ofStreptomyces spheroides NCIMB 11891.Antimicrob.Agents Chemother. 44, 1214–1222 (2000).
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This work was supported by theCzech Science Foundation, grants GA204/04/0801 and GA204/05/0616, and byInstitutional Research Concept of the Institute of Microbiology, Academy of Sciences of the Czech Republic, no. AV 0Z 5020 0510.
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Čermák, L., Novotná, J., Ságová-Marečková, M. et al. Hybridization analysis and mapping of the celesticetin gene cluster revealed genes shared with lincomycin biosynthesis. Folia Microbiol 52, 457–462 (2007). https://doi.org/10.1007/BF02932104
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DOI: https://doi.org/10.1007/BF02932104