Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지

sanN Encoding a Dehydrogenase is Essential for Nikkomycin Biosynthesis in Streptomyces ansochromogenes

  • Ling, Hong-Bo (State Key Laboratory of Microbial Resources, Institute of Microbiology, Chineses Academy of Sciences) ;
  • Wang, Guo-Jun (State Key Laboratory of Microbial Resources, Institute of Microbiology, Chineses Academy of Sciences) ;
  • Li, Jin-E (State Key Laboratory of Microbial Resources, Institute of Microbiology, Chineses Academy of Sciences) ;
  • Tan, Hua-Rong (State Key Laboratory of Microbial Resources, Institute of Microbiology, Chineses Academy of Sciences)
  • Published : 2008.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Nikkomycins are a group of peptidyl nucleoside antibiotics with potent fungicidal, insecticidal, and acaricidal activities. sanN was cloned from the partial genomic library of Streptomyces ansochromogenes 7100. Gene disruption and complementation analysis demonstrated that sanN is essential for nikkomycin biosynthesis in S. ansochromogenes. Primer extension assay indicated that sanN is transcribed from two promoters (sanN-P1 and sanN-P2), and sanN-P2 plays a more important role in nikkomycin biosynthesis. Purified recombinant SanN acts as a dehydrogenase to convert benzoate-CoA to benzaldehyde in a random-order mechanism in vitro, with respective $K_{cat}/K_m$$ values of $3.8mM^{-1}s^{-1}\;and\;12.0mM^{-1}s^{-1}$ toward benzoate-CoA and NADH, suggesting that SanN catalyzes the formation of picolinaldehyde during biosynthesis of nikkomycin X and Z components in the wild-type stain. These data would facilitate us to understand the biosynthetic pathway of nikkomycins and to consider the combinatorial synthesis of novel antibiotic derivatives.

Keywords

References

  1. Aemprapa, S. and P. A. Williams. 1998. Implications of the xylQ gene of TOL plasmid pWW102 for the evolution of aromatic catabolic pathways. Microbiology 144: 1387-1396 https://doi.org/10.1099/00221287-144-5-1387
  2. Altschul, S. F., T. L. Madden, A. A. Schaffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman. 1997. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res. 25: 3389-3402 https://doi.org/10.1093/nar/25.17.3389
  3. Arai, H., S. Akahira, T. Ohishi, M. Maeda, and T. Kudo. 1998. Adaptation of Comamonas testosteroni TA441 to utilize phenol: Organization and regulation of the genes involved in phenol degradation. Microbiology 144: 2895-2903 https://doi.org/10.1099/00221287-144-10-2895
  4. Arai, H., T. Ohishi, M. Y. Chang, and T. Kudo. 2000. Arrangement and regulation of the genes for meta-pathway enzymes required for degradation of phenol in Comamonas testosteroni TA441. Microbiology 146: 1707-1715 https://doi.org/10.1099/00221287-146-7-1707
  5. Bierman, M., R. Logan, K. O'Brien, E. T. Seno, R. N. Rao, and B. E Schoner. 1992. Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116: 43-49 https://doi.org/10.1016/0378-1119(92)90627-2
  6. Bormann, C., A. Kalmanczhelyi, R. Sussmuth, and G. Jung. 1999. Production of nikkomycins Bx and Bz by mutasynthesis with genetically engineered Streptomyces tendae Tu901. J. Antibiot. (Tokyo) 52: 102-108 https://doi.org/10.7164/antibiotics.52.102
  7. Bormann, C., S. Mattern, H. Schrempf, H. P. Fiedler, and H. Zahner. 1989. Isolation of Streptomyces tendae mutants with an altered nikkomycin spectrum. J. Antibiot. (Tokyo) 42: 913-918 https://doi.org/10.7164/antibiotics.42.913
  8. Brillinger, G. U. 1979. Metabolic products of microorganisms. 181. Chitin synthase from fungi, a test model for substances with insecticidal properties. Arch. Microbiol. 121: 71-74 https://doi.org/10.1007/BF00409207
  9. Bruntner, C. and C. Bormann. 1998. The Streptomyces tendae Tu901 L-lysine 2-aminotransferase catalyzes the initial reaction in nikkomycin D biosynthesis. Eur. J. Biochem. 254: 347-355 https://doi.org/10.1046/j.1432-1327.1998.2540347.x
  10. Bruntner, C., B. Lauer, W. Schwarz, V. Mohrle, and C. Bormann. 1999. Molecular characterization of co-transcribed genes from Streptomyces tendae Tu901 involved in the biosynthesis of the peptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin. Mol. Gen. Genet. 262: 102-114
  11. Chen, W., H. Zeng, and H. Tan. 2000. Cloning, sequencing, and function of sanF: A gene involved in nikkomycin biosynthesis of Streptomyces ansochromogenes. Curr. Microbiol. 41: 312-316 https://doi.org/10.1007/s002840010141
  12. Engel, P. and A. H. Ullah. 1988. Mutation affecting peptide bond formation in nikkomycin biosynthesis. Biochem. Biophys. Res. Commun. 156: 695-700 https://doi.org/10.1016/S0006-291X(88)80898-2
  13. Fiedler, H. P., R. Kurth, J. Langharig, J. Delzer, and H. Zahner. 1982. Nikkomycins: Microbial inhibitors of chitin synthetase. J. Chem. Technol. Biotechnol. 32: 271-280 https://doi.org/10.1002/jctb.5030320130
  14. Fiedler, H. P., T. Schuz, and H. Decker. 1993. An overview of nikkomycins: History, biochemistry, and applications, pp. 325-352. In J. W. Rippon and R. A. Fromtling (eds.), Cutaneous Antifungal Agents. Marcel Dekker Inc., N.Y.
  15. Kieser, T., M. J. Bibb, M. J. Buttner, K. F. Chater, and D. A. Hopwood. 2000. Practical Streptomyces Genetics. The John Innes Foundation, Norwich, U.K
  16. Li, W. and H. Tan. 2003. Structure and function of sanV: A gene involved in nikkomycin biosynthesis of Streptomyces ansochromogenes. Curr. Microbiol. 46: 403-407 https://doi.org/10.1007/s00284-002-3892-5
  17. Ling, H., G. Wang, Y. Tian, G. Liu, and H. Tan. 2007. SanM catalyzes the formation of 4-pyridyl-2-oxo-4-hydroxyisovalerate in nikkomycin biosynthesis by interacting with SanN. Biochem. Biophys. Res. Commun. 361: 196-201 https://doi.org/10.1016/j.bbrc.2007.07.016
  18. Liu, G., Y. Tian, H. Yang, and H. Tan. 2005. A pathway-specific transcriptional regulatory gene for nikkomycin biosynthesis in Streptomyces ansochromogenes that also influences colony development. Mol. Microbiol. 55: 1855-1866 https://doi.org/10.1111/j.1365-2958.2005.04512.x
  19. MacNeil, D. J., K. M. Gewain, C. L. Ruby, G. Dezeny, P. H. Gibbons, and T. MacNeil. 1992. Analysis of Streptomyces avermitilis genes required for avermectin biosynthesis utilizing a novel integration vector. Gene 111: 61-68 https://doi.org/10.1016/0378-1119(92)90603-M
  20. Miyazawa, D., G. Mukerjee-Dhar, M. Shimura, T. Hatta, and K. Kimbara. 2004. Genes for Mn(II)-dependent NahC and Fe(II)-dependent NahH located in close proximity in the thermophilic naphthalene and PCB degrader, Bacillus sp. JF8: Cloning and characterization. Microbiology 150: 993-1004 https://doi.org/10.1099/mic.0.26858-0
  21. Niu, G., G. Liu, Y. Tian, and H. Tan. 2006. SanJ, an ATPdependent picolinate-CoA ligase, catalyzes the conversion of picolinate to picolinate-CoA during nikkomycin biosynthesis in Streptomyces ansochromogenes. Metab. Eng. 8: 183-195 https://doi.org/10.1016/j.ymben.2005.12.002
  22. Paget, M. S., L. Chamberlin, A. Atrih, S. J. Foster, and M. J. Buttner. 1999. Evidence that the extracytoplasmic function sigma factor sigmaE is required for normal cell wall structure in Streptomyces coelicolor A3(2). J. Bacteriol. 181: 204-211
  23. Sambrook, J., E. F. Fritsch, and T. Maniatis. 2001. Molecular Cloning: A Laboratory Manual, 3rd Ed. Cold Spring Harbor, Laboratory Press, Cold Spring Harbor, N.Y.
  24. Shingler, V., J. Powlowski, and U. Marklund. 1992. Nucleotide sequence and functional analysis of the complete phenol/3,4-dimethylphenol catabolic pathway of Pseudomonas sp. strain CF600. J. Bacteriol. 174: 711-724 https://doi.org/10.1128/jb.174.3.711-724.1992
  25. Strohl, W. R. 1992. Compilation and analysis of DNA sequences associated with apparent streptomycete promoters. Nucleic Acids Res. 20: 961-974 https://doi.org/10.1093/nar/20.5.961
  26. Venci, D., G. Zhao, and M. S. Jorns. 2002. Molecular characterization of NikD, a new flavoenzyme important in the biosynthesis of nikkomycin antibiotics. Biochemistry 41:15795-15802 https://doi.org/10.1021/bi020515y