Contact us
닫기
Article Search
닫기

Microbiology and Biotechnology Letters

보문(Article)

View PDF

Molecular and Cellular Microbiology / Biomedical Sciences  |  Molecular Genetics, Omics, and Systems Biology

Microbiol. Biotechnol. Lett. 2016; 44(3): 391-399

https://doi.org/10.4014/mbl.1606.06008

Received: June 28, 2016; Accepted: August 23, 2016

Myxococcus stipitatus DSM 14675의 melithiazol 생합성 유전자 분석

Analysis of the Melithiazol Biosynthetic Gene Cluster in Myxococcus stipitatus DSM 14675

Hyesook Hyun 1, Soohyun Park 1 and Kyungyun Cho 1*

Department of Biotechnology, Hoseo University, Asan 31499, Republic of Korea

Abstract

Go to

Melithiazols are antifungal substances produced by the myxobacteria Melitangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. Melithiazol biosynthetic genes have been identified in M. lichenicola, but not in A. gephyra and M. stipitatus until now. We identified a 37.3-kb melithiazol biosynthetic gene cluster from M. stipitatus DSM 14675 using genome sequence analysis and mutational analysis. The cluster is comprised of 9 genes (MYSTI_04973 to MYSTI_04965) that encode 4 polyketide synthase modules, 3 nonribosomal peptide synthase modules, a putative fumarylacetoacetate hydrolase, a putative S-adenosylmethionine- dependent methyltransferase, and a putative nitrilase. Disruption of the MYSTI_04972 or MYSTI_ 04973 gene by plasmid insertion resulted in defective melithiazol production. The organization of the melithiazol biosynthetic modules encoded by 8 genes from MYSTI_04972 to MYSTI_04965 was similar to that in M. lichenicola Me l46. However, the loading module encoded by the first gene (MYSTI_04973) was different from that of M. lichenicola Me l46, explaining the difference in the production of melithiazol derivatives between the M. lichenicola Me l46 and M. stipitatus strains.

Keywords: Myxococcus stipitatus, myxobacteria, melithiazol

References

Go to
  1. An D, Park S, Lee JS, Cho K. 2014. Production of bioactive substances by a myxobacterium Myxococcus stipitatus KYC4013. Kor. J. Microbiol. Biotechnol. 42: 331–338.
    CrossRef
  2. Blin K, Medema MH, Kazempour D, Fischbach MA, Breitling R, Takano E, Weber T. 2013. antiSMASH 2.0 — a versatile platform for genome mining of secondary metabolite producers. Nucl. Acids Res. 41: W204-W212.
    Pubmed KoreaMed CrossRef
  3. Böhlendorf B, Herrmann M, Hecht H, Sasse F, Forche E, Kunze B, et al. 1999. Antibiotics from gliding bacteria, 85 Melithiazols A–N: new antifungal α-methoxyacrylates from myxobacteria. Eur. J. Org. Chem. 1999: 2601-2608.
    CrossRef
  4. Feng Z, Qi J, Tsuge T, Oba Y, Kobayashi T, Suzuki Y, et al. 2005. Construction of a bacterial artificial chromosome library for a myxobacterium of the genus Cystobacter and characterization of an antibiotic biosynthetic gene cluster. Biosci. Biotechnol. Biochem. 69: 1372-1380.
    Pubmed CrossRef
  5. Hagen DC, Bretscher AP, Kaiser D. 1978. Synergism between morphogenetic mutants of Myxococcus xanthus. Dev. Biol. 64:284-296.
    CrossRef
  6. Huntley S, Kneip S, Treuner-Lange A, Søgaard-Andersen L. 2013. Complete genome sequence of Myxococcus stipitatus strain DSM 14675, a fruiting myxobacterium. Genome Announc. 1:e0010013.
    Pubmed KoreaMed CrossRef
  7. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, et al. 2007. Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947-2948.
    Pubmed CrossRef
  8. Marchler-Bauer A, Derbyshire MK, Gonzales NR, Lu S, Chitsaz F, Geer LY, et al. 2015. CDD: NCBI's conserved domain database. Nucl. Acids Res. 43: D222-D226.
    Pubmed KoreaMed CrossRef
  9. Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, et al. 2011. antiSMASH: Rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters. Nucleic Acids Res. 39: W339-W346.
    Pubmed KoreaMed CrossRef
  10. Minowa Y, Araki M, Kanehisa M. 2007. Comprehensive analysis of distinctive polyketide and nonribosomal peptide structural motifs encoded in microbial genomes. J. Mol. Biol. 368: 1500–1517.
    Pubmed CrossRef
  11. Müller I, Müller R. 2006. Biochemical characterization of MelJ and MelK. FEBS J. 273: 3768-3778.
    Pubmed CrossRef
  12. Ojika M, Suzuki Y, Tsukamoto A, Sakagami Y, Fudou R, Yoshimura T, et al. 1998. Cystothiazoles A and B, new bithiazole-type antibiotics from the myxobacterium Cystobacter fuscus. J. Antibiot. 51:275-281.
    Pubmed CrossRef
  13. Reichenbach H. 2005. Myxococcales. pp. 1059-1144. In Brenner DJ, Krieg NR, Staley JT, Garrity GM (ed.), Bergey's Manual of Systematic Bacteriology, 2nd ed. Bergey's Manual Trust, East Lansing, MI., USA.
  14. Sasse F, Böhlendorf B, Herrmann M, Kunze B, Forche E, Steinmetz H, et al. 1999. Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties. J. Antibiot. 52: 721-729.
    Pubmed CrossRef
  15. Shin H, Youn J, An D, Cho K. 2013. Production of antimicrobial substances by strains of myxobacteria Corallococcus and Myxococcus. Korean J. Microbiol. Biotechnol. 41: 44–51.
    CrossRef
  16. Silakowski B, Schairer HU, Ehret H, Kunze B, Weinig S, Nordsiek G, et al. 1999. New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/3-1. J. Biol. Chem. 274: 37391-37399.
    Pubmed CrossRef
  17. Suzukia Y, Ojikaa M, Sakagamia Y, Fudou R, Yamanaka S. 1998. Cystothiazoles C-F, new bithiazole-type antibiotics from the myxobacterium Cystobacter fuscus. Tetrahedron 54: 11399–11404.
    CrossRef
  18. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. 2013. MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol. Biol. Evol. 30: 2725-2729.
    Pubmed KoreaMed CrossRef
  19. Trowitzsch W, Reifenstahl G, Wray V, Gerth K. 1980. Myxothiazol, an antibiotic from Myxococcus fulvus (myxobacterales). II. structure elucidation. J. Antibiot. 33: 1480-1490.
    Pubmed CrossRef
  20. Weinig S, Hecht HJ, Mahmud T, Müller R. 2003. Melithiazol biosynthesis:further insights into myxobacterial PKS/NRPS systems and evidence for a new subclass of methyl transferases. Chem. Biol. 10: 939-952.
    Pubmed CrossRef
  21. Weissman KJ, Müller R. 2010. Myxobacterial secondary metabolites:bioactivities and modes-of-action. Nat. Prod. Rep. 27: 12761295.
    Pubmed CrossRef
  22. Williams GJ. 2013. Engineering polyketide synthases and nonribosomal peptide synthetases. Curr. Opin. Struct. Biol. 23: 603612.
    Pubmed KoreaMed CrossRef
  23. Yadav G, Gokhale RS, Mohanty D. 2003. Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases. J. Mol. Biol. 328:335–363.
    CrossRef

Article Tools

Starts of Metrics

Share this article on :

Related articles in MBL

Most Searched Keywords ?

What is Most Searched Keywords?

  • It is most registrated keyword in articles at this journal during for 2 years.