Metabolism of herbicides and other chemicals in human cytochrome P450 species and in transgenic potato plants co-expressing human CYP1A1, CYP2B6 and CYP2C19

Metabolism of 50 herbicides and 7 other chemicals with different structures and modes of action was examined in the microsomes from the recombinant ye ast strains expressing each of ii human P450 species. Of these, 27 herbicid es and 6 other chemicals were mainly metabolized by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2D6 and CYP3A4. The metabolites of atrazine ( AT), chlortoluron (CT), fenitrothion (FT), methoxychlor (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 derivativ es. Based on these results, three major P450 species CYP1A1, CYP2B6 and CYP 2C19 in different families and subfamilies were selected and then co-expres sed in the transgenic potato plant T1977, which showed cross-tolerance towa rd the herbicides acetochlor (AC), AT, CT, methabenzthiazuron (MT), metolac hlor (MC), norflurazon (NR) and PC.(1)) The T1977 plant showed a higher act ivity in the metabolism of each of [C-14] CT, [C-14] AT, [C-14] PC and [C-1 4] MXC than the control. In T1977, [C-14] PC was almost completely metaboli zed to m-tert-butylphenol(BP), O-demethylated PC (DMPC), hydrox ylated BP ( BPOH) and unknown metabolites. Also, [C-14] MXC was rapidly metabolized in T1977 through O-demethylation to yield mono-demethylated and di-demethyrate d metabolites, which were mainly deposited as glucosides in the plants. The se results strongly suggested that three P450 species expressed in T1977 co ordinately functioned and actively metabolized the herbicides and the insec ticide. The transgenic plants expressed human P450 species metabolizing xen obiotics seem to be useful for generation of transgenic crops with low pest icide residues as well as for phytoremediation of pesticide residues.