Skip to main content
SpringerLink
Log in

Sequence analysis and heterologous expression of the lincomycin biosynthetic cluster of the type strain Streptomyces lincolnensis ATCC 25466

  • Papers
  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

A cosmid bearing an insert of 38 217 bp covering the gene cluster and its flanking regions of type strain Streptomyces lincolnensis ATCC 25466 was sequenced. Two relatively extensive sequence changes and several hundred point mutations were identified if compared with the previously published sequence of the lincomycin (Lin) industrial strain S. lincolnensis 78-11. Analysis of the cluster-flanking regions revealed its localization within the genome of the ATCC 25466 strain. The cluster-bearing cosmid was integrated into the chromosome of Lin non-producing strains S. coelicolor CH 999 and S. coelicolor M 145. The modified strains heterologously produced Lin but the level dropped to ≈1–3 % of the production in the ATCC 25466 strain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ABC:

ATP-binding cassette

Mtl:

methylthiolincosamide

l-Dop:

3,4-dihydroxy-L-phenylalanine

Ndl:

N-demethyllincomycin

int :

integrase gene of phage φC31

NDLS:

N-demethyllincomycin synthetase

Lin:

lincomycin

PCR:

polymerase chain reaction

lmb :

Lin biosynthetic genes

Ppl:

4-propyl-L-proline

MS:

mass spectrometry

UPLC:

ultra performance liquid chromatography

References

  • Altschul S.F., Madden T.L., Schaffer A.A., Zhang J., Zhang Z., Miller W., Lipman D.J.: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl.Acids Res. 25, 3389–3402 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Baltz R.H.: Genetic manipulation of antibiotic-producing Streptomyces. Trends Microbiol. 6, 76–83 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Čermák L., Novotná J., Ságová-Marečková M., Kopecký J., Najmanová L., Janata J.: Hybridization analysis and mapping of the celesticetin gene cluster revealed genes shared with lincomycin biosynthesis. Folia Microbiol. 52, 457–462 (2007).

    Article  Google Scholar 

  • Chung S.T., Manis J.J., Mcwethy J., Patt T.E., Witz D.F., Wolf H.J., Wovcha M.G.: Fermentation, biosynthesis and molecular genetics of lincomycin. Drugs Pharm.Sci. 82, 165–186 (1997).

    CAS  Google Scholar 

  • Combes P., Till R., Bee S., Smith M.C.: The Streptomyces genome contains multiple pseudo-attB sites for the (φ)C31-encoded sitespecific recombination system. J.Bacteriol. 184, 5746–5752 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Eustáquio A.S., Gust B., Galm U., Li S.M., Chater K.F., Heide L.: Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters. Appl.Environ.Microbiol. 71, 2452–2459 (2005).

    Article  PubMed  Google Scholar 

  • Flett F., Mersinias V., Smith C.P.: High efficiency intergeneric conjugal transfer of plasmid DNA from Escherichia coli to methyl DNA-restricting streptomycetes. FEMS Microbiol.Lett. 155, 223–229 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Gust B., Chandra G., Jakimowicz D., Yuqing T., Bruton C.J., Chater K.F.: γ-Red-mediated genetic manipulation of antibioticproducing Streptomyces. Adv.Appl.Microbiol. 54, 107–128 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Hu Y., Phelan V., Ntai I., Farnet C.M., Zazopoulos E., Bachmann B.O.: Benzodiazepine biosynthesis in Streptomyces refuineus. Chem.Biol. 14, 691–701 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Janata J., Najmanová L., Novotná J., Holá K., Felsberg J., Spížek J.: Putative lmbI and lmbH genes form a single lmbIH ORF in Streptomyces lincolnensis type strain ATCC 25466. Antonie van Leeuwenhoek 79, 277–284 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki T., Hayashi Y., Kuzuyama T., Furihata K., Itoh N., Seto H., Dairi T.: Biosynthesis of a natural polyketide-isoprenoid hybrid compound, furaquinocin A: identification and heterologous expression of the gene cluster. J.Bacteriol. 188, 1236–1244 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Kieser H.M., Buttner M.J., Chater K.F., Hopwood D.A.: Practical Streptomyces Genetics. John Innes Foundation, Norwich (UK) 2000.

    Google Scholar 

  • Kuo M.S., Yurek D.A., Coats J.H., Li G.P.: Isolation and identification of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, an unusual cosynthetic factor in streptomycetes, from Streptomyces lincolnensis. J.Antibiot.(Tokyo) 42, 475–478 (1989).

    CAS  Google Scholar 

  • Mcdaniel R., Ebert-Khosla S., Hopwood D.A., Khosla C.: Engineered biosynthesis of novel polyketides. Science 262, 1546–1550 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Neusser D., Schmidt H., Spíž’ek J., Novotná J., Peschke U., Kaschabeck S., Tichý P., Piepersberg W.: The genes lmbB1 and lmbB2 of Streptomyces lincolnensis encode enzymes involved in the conversion of L-tyrosine to propylproline during the biosynthesis of the antibiotic lincomycin A. Arch.Microbiol. 169, 322–332 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Novotná G., Janata J.: A new evolutionary variant of the streptogramin A resistance protein, Vga(A)LC, from Staphylococcus haemolyticus with shifted substrate specificity towards lincosamides. Antimicrob.Agents Chemother. 50, 4070–4076 (2006).

    Article  PubMed  Google Scholar 

  • 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).

    Article  PubMed  Google Scholar 

  • Olšovská J., Jelínková M., Man P., Koběrská M., Janata J., Flieger M.: High-throughput quantification of lincomycin traces in fermentation broth of genetically modified Streptomyces spp. Comparison of ultra-performance liquid chromatography and high-performance liquid chromatography with UV detection. J.Chromatogr.A 1139, 214–220 (2007).

    Article  PubMed  Google Scholar 

  • Onaka H., Taniguchi S., Igarashi Y., Furumai T.: Cloning of the staurosporine biosynthetic gene cluster from Streptomyces sp. TP-A0274 and its heterologous expression in Streptomyces lividans. J.Antibiot.(Tokyo) 55, 1063–1071 (2002).

    CAS  Google Scholar 

  • Penn J., Li X., Whiting A., Latif M., Gibbon T., Silva C.J., Brian P., Davies J., Miao V., Wrigley S.K., Baltz R.H.: Heterologous production of daptomycin in Streptomyces lividans. J.Ind.Microbiol.Biotechnol. 33, 121–128 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Peschke U., Schmidt H., Zhang H.Z., Piepersberg W.: Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78–11. Mol.Microbiol. 16, 1137–1156 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Velasco A., Acebo P., Gomez A., Schleissner C., Rodriguez P., Aparicio T., Conde S., Munoz R., De La Calle F., Garcia J.L., Sanchez-Puelles J.M.: Molecular characterization of the safracin biosynthetic pathway from Pseudomonas fluorescens A2-2: designing new cytotoxic compounds. Mol.Microbiol. 56, 144–154 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Widdick D.A., Dodd H.M., Barraille P., White J., Stein T.H., Chater K.F., Gasson M.J., Bibb M.J.: Cloning and engineering of the cinnamycin biosynthetic gene cluster from Streptomyces cinnamoneus DSM 40005. Proc.Nat.Acad.Sci.USA 100, 4316–4321 (2003).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Microbiology of the Academy of Sciences of the Czech Republic, v.v.i., 142 20, Prague, Czech Republic

    M. Koběrská, J. Kopecký, J. Olšovská, M. Jelínková, D. Ulanova, P. Man, M. Flieger & J. Janata

Authors
  1. M. Koběrská
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Kopecký
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Olšovská
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Jelínková
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Ulanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Man
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Flieger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Janata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Koběrská.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koběrská, M., Kopecký, J., Olšovská, J. et al. Sequence analysis and heterologous expression of the lincomycin biosynthetic cluster of the type strain Streptomyces lincolnensis ATCC 25466. Folia Microbiol 53, 395–401 (2008). https://doi.org/10.1007/s12223-008-0060-8

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12223-008-0060-8

Keywords

Search

Navigation