Difference between revisions of "Team:Goettingen/Background"

The discovery of the weedkiller glyphosate

Glyphosate (N-(phosphonomethyl)glycine) was first synthesized by the chemist Dr. Henri Martin in 1950, while working for the Swiss pharmaceutical company Cilag, which was founded in 1936 in Schaffhausen. About 20 years later, the American chemist Dr. John E. Franz who was working for the American company Monsanto (recently bought by Bayer) found out that glyphosate specifically inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase in plants, fungi, bacteria and archaea (Figure 1) (1-4). The EPSP synthase generates the precursor for the de novo synthesis of aromatic amino acids tryptophan, tyrosine and phenylalanine (5). Therefore, inhibition of the EPSP synthase by glyphosate results in the depletion of the cellular levels of aromatic amino acids and death of the organism that is treated with the weedkiller (Figure 1).

Figure 1. Glyphosate that is present in Roundup specifically inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase (PDBid: 2QFU), which converts shipmate-3-phosphate (S3P) and phosphoenolpyruvate (PEP) to EPSP. A drop in the cellular levels of the precursor for aromatic amino acid synthesis causes death of the organism that has been treated with Roundup.

The usage of glyphosate

Glyphosate is resistant to chemical hydrolysis, thermal decomposition and photolysis due to a stable C-P bond (2). Moreover, due to the fact that glyphosate is toxicologically safe and that transgenic, glyphosate-resistant crops have been introduced by Monsanto, the herbicide has become the dominant weedkiller worldwide (3-6). The production and usage rate of Glyphosate increasing up to this day (Figure 2). Moreover, given the fact that genetically modified crops that produce glyphosate-insensitive EPSP synthases are tolerated in the united states, glyphosate is the most used herbicide in this country (7).

Figure 2. Glyphosate usage over the last two decades. It has been estimated that the production of glyphosate is increasing with a rate of about 40 tons/year.

References

1. Amrhein et al. (1983) FEBS Lett. 157: 191-196.
2. Comai et al. (1983) Science 221: 370-371.
3. Schulz et al. (1984) Arch. Microbiol. 137: 121-123
4. Steinrücken & Amrhein (1980) Biochem. Biophys. Res. Commun. 94: 1207-1212.
5. Herrmann & Weaver (1999) Annu. Rev. Plant. Physiol. Plant. Mol. Biol. 50: 473-503.