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Metabolism of 50 herbicides and 7 other chemicals with different structures and modes of action was examined in the microsomes from the recombinant yeast strains expressing each of 11 human P450 species. Of these, 27 herbicides and 6 other chemicals were mainly metabolized by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C 18, CYP2C 19, CYP2D6 and CYP3A4. The metabolites of atrazine (AT), chlortoluron (CT), fenitrothion (FT), methoxychior (MXC), pyributicarb (PC), simazine (SZ) and simetryn (ST) were identified by co-chromatography with the authentic standards as well as LC/MS and GC/MS of their derivatives. Based on these results, three major P450 species CYP1A1, CYP2B6 and CYP2C19 in different families and subfamilies were selected and then co-expressed in the transgenic potato plant T1977, which showed cross-tolerance toward the herbicides acetochlor (AC), AT, CT, methabenzthiazuron (MT), metolachlor (MC), norflurazon (NR) and PC. ' The T1977 plant showed a higher activity in the metabolism of each of [14C] CT, [14C] AT, [14C] PC and [14C] MXC than the control. In T1977, [14C] PC was almost completely metabolized to m-tent-butylphenol(BP), 0-demethylated PC (DMPC), hydroxylated BP (BPOH) and unknown metabolites. Also, [14C] MXC was rapidly metabolized in T1977 through 0-demethylation to yield mono-demethylated and di-demethylated metabolites, which were mainly deposited as glucosides in the plants. These results strongly suggested that three P450 species expressed in T1977 coordinately functioned and actively metabolized the herbicides and the insecticide. The transgenic plants expressed human P450 species metabolizing xenobiotics seem to be useful for generation of transgenic crops with low pesticide residues as well as for phytoremediation of pesticide residues.

nippon nōyaku gakkaishi

Metabolism of Herbicides and Other Chemicals in Human Cytochrome P450 Species and in Transgenic Potato Plants Co-Expressing Human CYP1A1, CYP2B6 and CYP2C19