Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Genetic and Functional Analyses of the DKxanthene Biosynthetic Gene Cluster from Myxococcus stipitatus DSM 14675

  • Hyun, Hyesook (Department of Biotechnology, Hoseo University) ;
  • Lee, Sunjin (Department of Biotechnology, Hoseo University) ;
  • Lee, Jong Suk (Biocenter, Gyeonggido Business and Science Accelerator (GBSA)) ;
  • Cho, Kyungyun (Department of Biotechnology, Hoseo University)
  • Received : 2018.02.26
  • Accepted : 2018.05.29
  • Published : 2018.07.28
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Abstract

DKxanthenes are a class of yellow secondary metabolites produced by myxobacterial genera Myxococcus and Stigmatella. We identified a putative 49.5 kb DKxanthene biosynthetic gene cluster from Myxococcus stipitatus DSM 14675 by genomic sequence and mutational analyses. The cluster consisted of 15 genes (MYSTI_06004-MYSTI_06018) encoding polyketide synthases, non-ribosomal peptide synthases, and proteins with unknown functions. Disruption of the genes by plasmid insertion resulted in defects in the production of yellow pigments. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analyses indicated that the yellow pigments produced by M. stipitatus DSM 14675 might be novel DKxanthene derivatives. M. stipitatus did not require DKxanthenes for the formation of heat-resistant viable spores, unlike Myxococcus xanthus. Furthermore, DKxanthenes showed growth inhibitory activity against the fungi Aspergillus niger, Candida albicans, and Rhizopus stolonifer.

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References

  1. Reichenbach H. 2005. Myxococcales, pp. 1059-1144. In Brenner DJ, Krieg NR, Staley JT, Garrity GM (eds.), Bergey's Manual of Systematic Bacteriology, 2nd Ed. Bergey's Manual Trust, East Lansing, MI, USA.
  2. Shimkets LJ, Dworkin M, Reichenbach H. 2006. The myxobacteria, pp. 31-115. In Dworkin M, Falkow S, Rosenberg E, Schleifer KH, Stackebrandt E (eds.), The Prokaryotes, Vol. 7. Springer, New York, NY, USA.
  3. Weissman KJ, Muller R. 2010. Myxobacterial secondary metabolites: bioactivities and modes-of-action. Nat. Prod. Rep. 27: 1276-1295. https://doi.org/10.1039/c001260m
  4. Herrmann J, Fayad AA, Muller R. 2017. Natural products from myxobacteria: novel metabolites and bioactivities. Nat. Prod. Rep. 34: 135-160. https://doi.org/10.1039/C6NP00106H
  5. Meiser P, Bode HB, Muller R. 2006. The unique DKxanthene secondary metabolite family from the myxobacterium Myxococcus xanthus is required for developmental sporulation. Proc. Natl. Acad. Sci. USA 103: 19128-19133. https://doi.org/10.1073/pnas.0606039103
  6. Meiser P, Weissman KJ, Bode HB, Krug D, Dickschat JS, Sandmann A, et al. 2008. DKxanthene biosynthesis - understanding the basis for diversity-oriented synthesis in myxobacterial secondary metabolism. Chem. Biol. 15: 771-781. https://doi.org/10.1016/j.chembiol.2008.06.005
  7. Burchard RP, Burchard AC, Parish JH. 1977. Pigmentation phenotype instability in Myxococcus xanthus. Can. J. Microbiol. 23: 1657-1662. https://doi.org/10.1139/m77-238
  8. Furusawa G, Dziewanowska K, Stone H, Settles M, Hartzell P. 2011. Global analysis of phase variation in Myxococcus xanthus. Mol. Microbiol. 81: 784-804. https://doi.org/10.1111/j.1365-2958.2011.07732.x
  9. Laue BE, Gill RE. 1995. Using a phase-locked mutant of Myxococcus xanthus to study the role of phase variation in development. J. Bacteriol. 177: 4089-4096. https://doi.org/10.1128/jb.177.14.4089-4096.1995
  10. Wenzel SC, Muller R. 2009. The impact of genomics on the exploitation of the myxobacterial secondary metabolome. Nat. Prod. Rep. 26: 1385-1407. https://doi.org/10.1039/b817073h
  11. Sasse F, Steinmetz H, Hofle G, Reichenbach H. 1993. Rhizopodin, a new compound from Myxococcus stipitatus (myxobacteria) causes formation of rhizopodia-like structures in animal cell cultures. Production, isolation, physico-chemical and biological properties. J. Antibiot. (Tokyo) 46: 741-748. https://doi.org/10.7164/antibiotics.46.741
  12. Sasse F, Bohlendorf B, Herrmann M, Kunze B, Forche E, Steinmetz H, et al. 1999. Melithiazols, new betamethoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties. J. Antibiot. (Tokyo) 52: 721-729. https://doi.org/10.7164/antibiotics.52.721
  13. Trowitzsch-Kienast W, Forche E, Wray V, Reichenbach H, Jurkiewicz E, Hunsmann G, Hofle G. 1992. Antibiotika aus gleitenden bakterien, 45. phenalamide, neue HIV-1-inhibitoren aus Myxococcus stipitatus Mx s40. Liebigs Ann. Chem. 1992: 659-779. https://doi.org/10.1002/jlac.1992199201112
  14. 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. https://doi.org/10.1093/nar/gkr466
  15. Weber T, Blin K, Duddela S, Krug D, Kim HU, Bruccoleri R, et al. 2015. antiSMASH 3.0 - a comprehensive resource for the genome mining of biosynthetic gene clusters. Nucleic Acids Res. 43: W237-W243. https://doi.org/10.1093/nar/gkv437
  16. Johnson M, Zaretskaya I, Raytselis Y, Mereshuk Y, McGinnis S, Madden TL. 2008. NCBI BLAST: a better web interface. Nucleic Acids Res. 36: W5-W9. https://doi.org/10.1093/nar/gkn201
  17. Marchler-Bauer A, Derbyshire MK, Gonzales NR, Lu S, Chitsaz F, Geer LY, et al. 2015. CDD: NCBI's conserved domain database. Nucleic Acids Res. 43: D222-D226. https://doi.org/10.1093/nar/gku1221
  18. Cho K, Zusman DR. 1999. Sporulation timing in Myxococcus xanthus is controlled by the espAB locus. Mol. Microbiol. 34: 714-725. https://doi.org/10.1046/j.1365-2958.1999.01633.x
  19. Shi W, Kohler T, Zusman DR. 1994. Motility and chemotaxis in Myxococcus xanthus. Methods Mol. Genet. 3: 258-269.
  20. 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. https://doi.org/10.4014/kjmb.1210.10011
  21. Zimbro MJ, Power DA, Miller SM, Wilson GE, Johnson JA (eds.). 2009. Difco and BBL Manual: Manual of Microbiological Culture Media, 2nd Ed. Becton Dickinson and Co., Sparks, MD, USA.
  22. Park S, Hyun H, Lee JS, Cho K. 2016. Identification of the phenalamide biosynthetic gene cluster in Myxococcus stipitatus DSM 14675. J. Microbiol. Biotechnol. 26: 1636-1642 https://doi.org/10.4014/jmb.1603.03023
  23. Huntley S, Kneip S, Treuner-Lange A, Sogaard-Andersen L. 2013. Complete genome sequence of Myxococcus stipitatus strain DSM 14675, a fruiting myxobacterium. Genome Announc. 1: e0010013. https://doi.org/10.1128/genomeA.00100-13
  24. Hyun H, Park S, Cho K. 2016. Analysis of the melithiazol biosynthetic gene cluster in Myxococcus stipitatus DSM 14675. Microbiol. Biotechnol. Lett. 44: 391-399. https://doi.org/10.4014/mbl.1606.06008
  25. Berdy J. 2012. Thoughts and facts about antibiotics: where we a re now and where we are heading . J. Antibiot. (Tokyo) 65: 385-395. https://doi.org/10.1038/ja.2012.27
  26. Schaberle TF, Lohr F, Schmitz A, Konig GM. 2014. Antibiotics from myxobacteria. Nat. Prod. Rep. 31: 953-972. https://doi.org/10.1039/c4np00011k
  27. Keane R, Berleman J. 2016. The predatory life cycle of Myxococcus xanthus. Microbiology 162: 1-11 https://doi.org/10.1099/mic.0.000208
  28. Dey A, Vassallo CN, Conklin AC, Pathak DT, Troselj V, Wall D. 2016. Sibling rivalry in Myxococcus xanthus is mediated by kin recognition and a polyploid prophage. J. Bacteriol. 198: 994-1004. https://doi.org/10.1128/JB.00964-15

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