Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Jan;35(1):170–173. doi: 10.1128/aac.35.1.170

Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins.

E Cabib 1
PMCID: PMC244960  PMID: 2014972

Abstract

Polyoxin D, nikkomycin X, and nikkomycin Z are all competitive inhibitors of chitin synthetase 2 (Chs2), the essential enzyme for primary septum formation in Saccharomyces cerevisiae, and of Chs1, a repair enzyme. However, Chs2 is more resistant to these antibiotics than Chs1. When Co2+, the best stimulator of Chs2, was used in the assay for this enzyme, the differences in the Ki values for nikkomycins between the two isozymes reached 3 orders of magnitude. These results point to differences in the active sites of the two isozymes. Polyoxin D was much more effective than nikkomycin Z in inhibiting cell growth. This underlines the importance of the choice of enzyme and of assay conditions when cell wall-synthesizing enzymes are used in screens for possible antifungal agents.

Full text

PDF
170

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Au-Young J., Robbins P. W. Isolation of a chitin synthase gene (CHS1) from Candida albicans by expression in Saccharomyces cerevisiae. Mol Microbiol. 1990 Feb;4(2):197–207. doi: 10.1111/j.1365-2958.1990.tb00587.x. [DOI] [PubMed] [Google Scholar]
  2. Bowers B., Levin G., Cabib E. Effect of polyoxin D on chitin synthesis and septum formation in Saccharomyces cerevisiae. J Bacteriol. 1974 Aug;119(2):564–575. doi: 10.1128/jb.119.2.564-575.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braun P. C., Calderone R. A. Chitin synthesis in Candida albicans: comparison of yeast and hyphal forms. J Bacteriol. 1978 Mar;133(3):1472–1477. doi: 10.1128/jb.133.3.1472-1477.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cabib E., Bowers B., Sburlati A., Silverman S. J. Fungal cell wall synthesis: the construction of a biological structure. Microbiol Sci. 1988 Dec;5(12):370–375. [PubMed] [Google Scholar]
  5. Cabib E., Sburlati A., Bowers B., Silverman S. J. Chitin synthase 1, an auxiliary enzyme for chitin synthesis in Saccharomyces cerevisiae. J Cell Biol. 1989 May;108(5):1665–1672. doi: 10.1083/jcb.108.5.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cabib E. The synthesis and degradation of chitin. Adv Enzymol Relat Areas Mol Biol. 1987;59:59–101. doi: 10.1002/9780470123058.ch2. [DOI] [PubMed] [Google Scholar]
  7. Duran A., Cabib E. Solubilization and partial purification of yeast chitin synthetase. Confirmation of the zymogenic nature of the enzyme. J Biol Chem. 1978 Jun 25;253(12):4419–4425. [PubMed] [Google Scholar]
  8. Dähn U., Hagenmaier H., Höhne H., König W. A., Wolf G., Zähner H. Stoffwechselprodukte von mikroorganismen. 154. Mitteilung. Nikkomycin, ein neuer hemmstoff der chitinsynthese bei pilzen. Arch Microbiol. 1976 Mar 19;107(2):143–160. doi: 10.1007/BF00446834. [DOI] [PubMed] [Google Scholar]
  9. Hori M., Eguchi J., Kakiki K., Misato T. Studies on the mode of action of polyoxins. VI. Effect of polyoxin B on chitin synthesis in polyoxin-sensitive and resistant strains of Alternaria kikuchiana. J Antibiot (Tokyo) 1974 Apr;27(4):260–266. doi: 10.7164/antibiotics.27.260. [DOI] [PubMed] [Google Scholar]
  10. Island M. D., Naider F., Becker J. M. Regulation of dipeptide transport in Saccharomyces cerevisiae by micromolar amino acid concentrations. J Bacteriol. 1987 May;169(5):2132–2136. doi: 10.1128/jb.169.5.2132-2136.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Isono K., Asahi K., Suzuki S. Studies on polyoxins, antifungal antibiotics. 13. The structure of polyoxins. J Am Chem Soc. 1969 Dec 17;91(26):7490–7505. doi: 10.1021/ja01054a045. [DOI] [PubMed] [Google Scholar]
  12. Kang M. S., Elango N., Mattia E., Au-Young J., Robbins P. W., Cabib E. Isolation of chitin synthetase from Saccharomyces cerevisiae. Purification of an enzyme by entrapment in the reaction product. J Biol Chem. 1984 Dec 10;259(23):14966–14972. [PubMed] [Google Scholar]
  13. Molano J., Bowers B., Cabib E. Distribution of chitin in the yeast cell wall. An ultrastructural and chemical study. J Cell Biol. 1980 May;85(2):199–212. doi: 10.1083/jcb.85.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Naider F., Shenbagamurthi P., Steinfeld A. S., Smith H. A., Boney C., Becker J. M. Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents. Antimicrob Agents Chemother. 1983 Nov;24(5):787–796. doi: 10.1128/aac.24.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Orlean P. Two chitin synthases in Saccharomyces cerevisiae. J Biol Chem. 1987 Apr 25;262(12):5732–5739. [PubMed] [Google Scholar]
  16. Sburlati A., Cabib E. Chitin synthetase 2, a presumptive participant in septum formation in Saccharomyces cerevisiae. J Biol Chem. 1986 Nov 15;261(32):15147–15152. [PubMed] [Google Scholar]
  17. Shenbagamurthi P., Smith H. A., Becker J. M., Naider F. Synthesis and biological properties of chitin synthetase inhibitors resistant to cellular peptidases. J Med Chem. 1986 May;29(5):802–809. doi: 10.1021/jm00155a034. [DOI] [PubMed] [Google Scholar]
  18. Silverman S. J., Sburlati A., Slater M. L., Cabib E. Chitin synthase 2 is essential for septum formation and cell division in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4735–4739. doi: 10.1073/pnas.85.13.4735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Silverman S. J. Similar and different domains of chitin synthases 1 and 2 of S. cerevisiae: two isozymes with distinct functions. Yeast. 1989 Nov-Dec;5(6):459–467. doi: 10.1002/yea.320050605. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES