Herbicides amino acid biosynthesis

J. Stetter (ed.), Herbicides Inhibiting Branched Chain Amino Acids Biosynthesis. Recent Development [Chemistry of Plant Protection, Vol. 10], Springer-Verlag, Berlin, 1994. 

Herbicide resistance is becoming a problem in many situations. The rush of compounds that interfere with branched chain amino acid biosynthesis has meant that a very high area of land has been treated with compounds that have the same mode of action. The application... 

Three herbicides considered to be safe. These compounds all act on an enzyme required for branched amino acid biosynthesis. Since this enzyme is not present in mammals, the herbicides are considered to be harmless to humans. 

In recent years, agribusiness firms have developed pf empirically several compounds that inhibit essential steps in the biosynthesis of amino acids found in plants but missing in animals. One of these compounds, glyphosate, is a highly specific inhibitor of 5-enol pyruvyl-shikimate-3-phosphate synthase (an enzyme needed for aromatic amino acid biosynthesis). Glyphosate is the active ingredient in the widely used herbicide Roundup. 

Three other classes of compounds, although quite different from each other, are all inhibitors of acetohydroxy acid synthase (an enzyme required for branched-chain amino acid biosynthesis (see fig. 21.10). These three classes are sulfonylureas, imidazolinones, and triazolpyrimidines, which are the active ingredients in, respectively, Oust, Sceptor, and a third commercial herbicide still under development (fig. 21.11). 

Kishore, G. M., and D. M. Shah, Amino acid biosynthesis inhibitors as herbicides. Ann. Rev. Biochem. 57 627-663,... 

Glyphosate is toxic to plants and free-living microorganisms because it inhibits aromatic amino acid biosynthesis. On the other hand, it is extremely nontoxic to humans and animals because humans derive their amino acids from the diet. Additionally, it is broken down in the soil, so it is non-persistent. The only problem with glyphosate herbicides is that they will kill crop plants as readily as weeds. Recently, genetically engineered crop varieties have been introduced which are resistant to the herbicide, allowing weeds to be killed preferentially. 

It is clear from the above discussion ensure that glyphosate tolerance may be conferred to plants both by overproduction of wild type EPSPS as well as mutant EPSP synthases. It has been suggested that glyphosate may have multiple sites of action in plant cells (51-56). If this is true, mutant EPSPS enzymes would not confer glyphosate tolerance to plants, which is evidently not the case. It appears, therefore, that reports concerning the effect of glyphosate on other aspects of plant metabolism are due to secondary effects of the herbicide arising as a consequence of the inhibition of aromatic amino acid biosynthesis. 

Another process of Importance to plant science Is amino acid biosynthesis. Plants and most microbes share the capacity to synthesize the twenty common amino acids from central, key metabolites (see Figure 1). In contrast animals must Ingest ten amino acids "essential to their diet they are unable to produce leucine, valine, Isoleuclne, threonine, methionine, lysine, histidine, tryptophan, tyrosine and phenylalanine. A sufficiently specific chemical Inhibiting the biosynthesis of an essential amino acid thus might control weed growth and display little toxicity towards mammals. Indeed a number of herbicides interfere with the biosynthesis of the essential amino acids (, see Table I). 

Table I. Herbicides Interfering with Essential Amino Acid Biosynthesis...

Higher animals tend to have limited biosynthetic abilities because their diet contains plants and sometimes other animals. Thus there are many amino acids which animals can t synthesize. One of the most popular herbicides in use today is glyphosate or Roundup, which inhibits the synthesis of phenylalanine. See page 679 in the text (Section 24.2.10) for more discussion. There are several herbicides that block amino acid biosynthesis. They are not very toxic to animals because they block enzymes we lack. 

Inhibitors of Acetolactate Synthase (ALS/AHAS) The enzyme acetolactate synthase (ALS) plays in plants an essential role in branched-chain amino acid biosynthesis. In the pathway leading to valine and leucine, ALS catalyzes the formation of 2-acetolactate from two pyruvate molecules, and in the pathway to isoleucine the formation of 2-acetohydroxybutyrate from 2-ketobutyrate and pyruvate. Due to this double function the enzyme is also called with a more general term aceto-hydroxyacid synthase. ALS is inhibited by several groups of herbicides, mainly the sulfonylureas (SUs), imidazolinones (IMIs), triazolopyrimidines (TPs), pyrimidinylthiobenzoates(PTBs) and sulfonylaminocarbonyltriazolinone (SCTs) (see Chapter 2.1, M. E. Thompson). 

J. Stetter (volume editor) Herbicides inhibiting branched-chain amino acid biosynthesis. Springer, Berlin Heidelberg, Volume 10, 47-81,... 

S. K. Gee, J. V. Hay, Recent developments in the chemistry of sulfonylurea herbicides, in W. Ebing (editor-in-chief) Chemistry of Plant Protection, J. Stetter (volume editor) Herbicides inhibiting branched-chain amino acid biosynthesis. Springer, Berlin Heidelberg, Volume 10, 15—46, (1994). 

Kleschick WA, Triazolopyrimidine Sulfonanilides and Related Compounds. In Herbicides Inhibiting Branch Chain Amino Acid Biosynthesis, Stetter, J. Ed., Spinger-Verlag, Germany, 1994, Vol. 10, pp 119-143. 

Derivatives of the dehydroshikimate analogue 1,6-dihydroxy-2-oxoisonicotinic acid (Fig. 4) were fairly powerful inhibitors of shikimate dehydrogenase from pea, but they failed as herbicides in vivo. There is a certain irony in the fact that in the same year in which Baillie et al. announced the inconclusive outcome of their efforts, Jaworski proposed inhibition of aromatic amino acid biosynthesis as the mode of action of glyphosate, which was just emerging as a highly successful herbicide. 

Imazaquin, an example of the imidazolinone class of herbicides, is particularly selective to soybeans. These compounds have a similar mode of action to that of the sulfonylurea herbicides, which will be discussed later. They block branched chain amino acid biosynthesis by inhibition of the enzyme acetolactate synthase (ALS). 

In considering the commercially successful herbicides known to be inhibitors of amino acid biosynthesis, three aspects will be considered the kinetic description of the inhibition, the molecular interactions involved, and the relevance of the proposed target site to the observed physiological effects. Because of the extensive body of research published on the shikimate pathway and the herbicide glyphosate, this example will be taken as a paradigm of the inhibitor-enzyme relationship. The other cases considered will be the branched-chain amino acid family, histidine biosynthesis, and glutamine synthetase. 

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