Identification and formation pattern of metabolites of cyazofamid by soil fungus Cunninghamella elegans

Abstract

This study was performed to investigate the formation of microbial metabolites from cyazofamid by the soil fungus Cunninghamella elegans. The incubation of cyazofamid with C. elegans was conducted for 10 days. Cyazofamid disappeared after 7 days of incubation, producing three metabolites. Metabolites identified by liquid chromatography–tandem mass spectrometry were 4-chloro-5-(4-(hydroxymethyl)phenyl)-imidazole-2-carbonitrile (CHCN), 4-(4-chloro-2-cyanoimidazole-5-yl)benzoic acid (CCBA) and 4-chloro-2-cyano-5-(4-(hydroxymethyl)phenyl)N,N-dimethyl-1H-imidazole-1-sulfonamide (CCHS). A new metabolite, CCHS, was further confirmed by 1H-13C HSQC (heteronuclear single-quantum correlation) using nuclear magnetic resonance. As a possible metabolic pathway, cyazofamid could be oxidized to CCHS, degraded to CHCN and further oxidized to CCBA. The metabolic system of C. elegans would be a powerful tool for predicting and identifying phase I metabolites that could be formed in mammalian systems.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Abass K, Reponen P, Mattila S, Rautio A, Pelkonen O (2014) Human variation and CYP enzyme contribution in benfuracarb metabolism in human in vitro hepatic models. Toxicol Lett 224:300–309

    CAS  Article  Google Scholar 

  2. Amadio J, Gordon K, Murphy CD (2010) Biotransformation of flurbiprofen by Cunninghamella species. Appl Environ Microbiol 76:6299–6303

    CAS  Article  Google Scholar 

  3. Asha S, Vidyavathi M (2009) Cunninghamella - A microbial model for drug metabolism studies: a review. Biotechnol Adv 27:16–29

    CAS  Article  Google Scholar 

  4. Choi JH, El-Aty AMA, Park YS, Cho SK, Shim JH (2007) The assessment of carbendazim, cyazofamid, diethofencarb and pyrimethanil residue levels in P-ginseng (C.A. Meyer) by HPLC. Bull Korean Chem Soc 28:369–372

    CAS  Article  Google Scholar 

  5. Evaluation Report Cyazofamid (2004) Food safety commission pesticides experts committee. https://www.fsc.go.jp/english/evaluationreports/pesticide/cyazofamid_fullreport.pdf

  6. Hangler M, Jensen B, Ronhede S, Sorensen SR (2007) Inducible hydroxylation and demethylation of the herbicide isoproturon by Cunninghamella elegans. FEMS Microbiol Lett 268:254–260

    CAS  Article  Google Scholar 

  7. Hodgson E, Rose RL (2008) Metabolic interactions of agrochemicals in humans. Pest Manag Sci 64:617–621

    CAS  Article  Google Scholar 

  8. Kang SI, Kang SY, Kanaly RA, Lee E, Lim Y, Hur HG (2009) Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus Cunninghamella elegans. Arch Microbiol 191:509–517

    CAS  Article  Google Scholar 

  9. Keum YS, Lee YH, Kim JH (2009) Metabolism of methoxychlor by Cunninghamella elegans ATCC36112. J Agric Food Chem 57:7931–7937

    CAS  Article  Google Scholar 

  10. Lee H et al (2012) Establishment of analytical method for cyazofamid residue in apple, mandarin, Korean cabbage, green pepper, potato and soybean. J Korean Soc Appl Biol Chem 55:241–247

    CAS  Article  Google Scholar 

  11. Lee H, Kim E, Lee JH, Sung JH, Choi H, Kim JH (2014) Analysis of cyazofamid and its metabolite in the environmental and crop samples using LC-MS/MS. Bull Environ Contam Toxicol 93:586–590

    CAS  Article  Google Scholar 

  12. Mitani S, Araki S, Takii Y, Ohshima T, Matsuo N, Miyoshi H (2001) The biochemical mode of action of the novel selective fungicide cyazofamid: specific inhibition of mitochondrial complex III in Phythium spinosum. Pestic Biochem Phys 71:107–115

    CAS  Article  Google Scholar 

  13. Moody JD, Zhang DL, Heinze TM, Cerniglia CE (2000) Transformation of amoxapine by Cunninghamella elegans. Appl Environ Microb 66:3646–3649

    CAS  Article  Google Scholar 

  14. Moody JD, Freeman JP, Fu PP, Cerniglia CE (2002) Biotransformation of mirtazapine by Cunninghamella elegans. Drug Metab Dispos 30:1274–1279

    CAS  Article  Google Scholar 

  15. Pestcide Fact Sheet Cyazofamid (2004). United States Environmental Protection Agency. http://www.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-085651_01-Sep-04.pdf

  16. Pothuluri JV, Freeman JP, Heinze TM, Beger RD, Cerniglia CE (2000) Biotransformation of vinclozolin by the fungus Cunninghamella elegans. J Agr Food Chem 48:6138–6148

    CAS  Article  Google Scholar 

  17. Rydevik A, Thevis M, Krug O, Bondesson U, Hedeland M (2013) The fungus Cunninghamella elegans can produce human and equine metabolites of selective androgen receptor modulators (SARMs). Xenobiotica 43:409–420

    CAS  Article  Google Scholar 

  18. Schocken MJ, Mao J, Schabacker DJ (1997) Microbial transformations of the fungicide cyprodinil (CGA-219417). J Agric Food Chem 45:3647–3651

    CAS  Article  Google Scholar 

  19. Singh N, Tandon S (2015) Dissipation kinetics and leaching of cyazofamid fungicide in texturally different agricultural soils. Int J Environ Sci Technol 12:2475–2484

    CAS  Article  Google Scholar 

  20. Slade M, Casida JE (1970) Metabolic fate of 3,4,5- and 2,3,5-trimethylphenyl methylcarbamates, the major constituents in Landrin insecticide. J Agric Food Chem 18:467–474

    CAS  Article  Google Scholar 

  21. Suzuki T, Casida JE (1981) Metabolites of diuron, linuron, and methazole formed by liver microsomal-enzymes and spinach plants. J Agric Food Chem 29:1027–1033

    CAS  Article  Google Scholar 

  22. Tandon S, Singh N (2015) Dissipation kinetics of cyazofamid in water. J Liq Chromatogr Relat Technol 38:993–996

    CAS  Article  Google Scholar 

  23. Tomlin C (2009) The pesticide manual: a world compendium, 15th edn. British Crop Protection Council, Alton

    Google Scholar 

  24. Tseng SH et al (2009) Analysis of 81 pesticides and metabolite residues in fruits and vegetables by diatomaceous earth column extraction and LC/MS/MS determination. J Food Drug Anal 17:319–332

    CAS  Google Scholar 

  25. Zhang DL, Evans FE, Freeman JP, Yang YF, Deck J, Cerniglia CE (1996) Formation of mammalian metabolites of cyclobenzaprine by the fungus, Cunninghamella elegans. Chem Biol Interact 102:79–92

    CAS  Article  Google Scholar 

  26. Zhu YZ, Keum YS, Yang L, Lee H, Park H, Kim JH (2010) Metabolism of a fungicide mepanipyrim by soil fungus Cunninghamella elegans ATCC36112. J Agric Food Chem 58:12379–12384

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jeong-Han Kim.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lee, H., Kim, E., Shin, Y. et al. Identification and formation pattern of metabolites of cyazofamid by soil fungus Cunninghamella elegans . Appl Biol Chem 59, 9–14 (2016). https://doi.org/10.1007/s13765-015-0127-6

Download citation

Keywords

  • Cunninghamella elegans
  • Cyazofamid
  • Liquid chromatography–tandem mass spectrometry
  • Metabolite
  • Nuclear magnetic resonance