Hydrolysis of individual isomers of fluorogenic pyrethroid analogs by mutant carboxylesterases from Lucilia cuprina

A. L. Devonshire, R. Heidari, H. Z. Huang, B. D. Hammock, R. J. Russell, J. G. Oakeshott

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

We previously showed that wild-type E3 carboxylesterase of Lucilia cuprina has high activity against Type 1 pyrethroids but much less for the bulkier, α-cyano containing Type 2 pyrethroids. Both Types have at least two optical centres and, at least for the Type 1 compounds, we found that wild-type E3 strongly prefers the less insecticidal configurations of the acyl group. However, substitutions to smaller residues at two sites in the acyl pocket of the enzyme substantially increased overall activity, particularly for the more insecticidal isomers. Here we extend these analyses to Type 2 pyrethroids by using fluorogenic analogs of all the diastereomers of cypermethrin and fenvalerate. Wild-type E3 hydrolysed some of these appreciably, but, again, not those corresponding to the most insecticidal isomers. Mutations in the leaving group pocket or oxyanion hole were again generally neutral or deleterious. However, the two sets of mutants in the acyl pocket again improved activity for the more insecticidal acyl group arrangements as well as for the more insecticidal configuration of the cyano moiety on the leaving group. The activities of the best mutant enzyme against the analogs of the most insecticidal isomers of cypermethrin and fenvalerate were more than ten and a hundred fold higher, respectively, than those of wild-type. The implications for resistance development are discussed.

Original languageEnglish (US)
Pages (from-to)891-902
Number of pages12
JournalInsect Biochemistry and Molecular Biology
Volume37
Issue number9
DOIs
StatePublished - Sep 2007

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Keywords

  • Esterases
  • In vitro mutagenesis
  • Insecticide
  • Isomers
  • Pyrethroid hydrolase
  • Resistance

ASJC Scopus subject areas

  • Insect Science
  • Biochemistry

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