Herbicides monooxygenase

The metabolism of 1,3,5-triazine herbicides containing chlorine substituents involves hydrolytic displacement of chloride (Cook 1987), although it seems not to have been established whether this is a hydroxylase or a monooxygenase. The halohydrolase from a strain of Pseudomonas sp. that uses atrazine as a nitrogen source has been cloned into Escherichia coli (de Souza et al. 1995), while the inducible enzyme that has been purified from R. corallinus (Mulbry 1994) is also capable of carrying out deamination of amino-substituted 1,3,5-triazines. 

T.J. Fleischmann, and R.E. Dewey (1999). Expression of a soybean cytochrome P450 monooxygenase cDNA in yeast and tobacco enhances the metabolism of phenylurea herbicides. Proc. Natl Acad. Sci USA 96, 1750-1755. 

NA had also a stimulatory effect on the oxidative metabolism of the herbicide bentazone. Microsomal preparations of etiolated shoots from maize, which had received a seed treatment with NA, showed activity of a bentazone hydroxylase, which was not detectable in extracts from controls without safener pre-treatment [35]. Also, the improved tolerance of maize to the imidazolinone AC263222 after NA seed treatment could be related to enhanced AC 263222 hydroxylation by stimulation of a cytochrome P450 monooxygenase [31]. 

Resistance to herbicides has been associated with a high capacity to metabolise these compounds. N-Demethylation, a first step in the deactivation of the phenyl-ureas, is thought to involve a cytochrome P-450 dependent oxygenase [16]. Some inhibitors of this reaction, including triazole derivatives, act synergistically with phenylurea herbicides by reducing their metabolism [7, 29]. The normal function of these monooxygenases is unknown, but could be one or more of the processes discussed above. There is also evidence that cytochrome P-450 activity can be induced in plants treated with some xenobiotics [25] and this may represent a natural defense mechanism. 

As the grass weeds in Table 2 evolved resistance to all the wheat selective herbicides, irrespective of their site of action, the most likely hypothesis is that they evolved the same biochemical detoxification mechanism as wheat, i.e. evolved a biochemical mimicry . This is supported by evidence that compounds that suppress the herbicide degradation in wheat also suppress their degradation. Little is known about the monooxygenases of wheat, and less is known about those in weeds, and presently not too much can be said. Still, it is clear from the data in Table 2 that biochemical mimicries need not be absolute. The weeds evolved spectra of cross resistances that are broader than the resistance in wheat. 

Table 4. The suppression of herbicide degradation by monooxygenase inhibitors...

The problem is selectivity to suppress herbicide degradation in the weeds but not in wheat. As the biochemical mimicries are not absolute, even small differences between monooxygenase systems can be amplified by synergists. By analogy we may consider that this may be possible. 

The oxidation of phenols to catechols or hydroquinones by tyrosinase enzymes has been developed for biocatalysis. For example, the ortho-hydroxylation of L-tyrosine 162 (and also substituted variants) to give l-DOPA 163 has been extensively studied due to the importance of l-DOPA in the treatment of Parkinson s disease [92, 93]. An arene hydroxy lating enzyme having a broad substrate scope is 2-hydroxybiphenyl 3-monooxygenase from Pseudomonas azelaica, which is able to oxidize many ortho-substituted phenols 68 to the corresponding catechols 127 [94], as shown in Scheme 32.19. A notable example of an industrial biocatalytic arene hydroxylation that has been employed on very large scale (lOOm fermentation) is the pora-hydroxylation of R)-2-phenoxypropionic acid 164 by whole cells of Beauveria bassiana Lu 700 to give (R)-2-(4-hydroxyphenoxy)propionic acid 165, an important intermediate in herbicide manufacture [95]. 

Cytochrome P450 monooxygenases (CYP) are membrane-bound enzymes that catalyze the addition of oxygen to hydrophobic compounds. CYPs are important enzymes in plant secondary metabolism however, they are also important in selectivity of a large numbor of hmbicides, particularly in cereals (70). CYPs catalyze a variety of reactions, but the most important ones for herbicide detoxification are hydroxylations and dealkylations (Figure 3). Ring hydroxylation reactions frequently render herbicides inactive however, dealkylation reactions may only partially detoxify herbicides. 

Figure 3. Examples of herbicide detoxification reactions catalyzed by cytochrome P450 monooxygenases.

---