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 company Monsanto (now Bayer) found out that glyphosate specifically inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase in plants, fungi, bacteria and archaea (Figure 1) (1). The EPSP synthase generates the precursor for the de novo synthesis of aromatic amino acids tryptophan, tyrosine and phenylalanine. 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, 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.

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 usage rate of Glyphosate has been ever increasing since its release and is still increasing up to this day, making it the most used herbicide in the USA.

Glyphosate usage over the last two decades. The increase can be described with a linear growing curve.

How does Glyphosate work?

Glyphosate targets the EPSP Synthase in the Shikimate pathway of plants and bacteria. This pathway is used to form essential aromatic amino acids, like Tyrosin, Phenylalanine and Tryptophane, which serve as building blocks for proteins and play a crucial role in metabolism. Amino acids are building blocks for proteins in every organism and thus have to be acquired through nutrition or generated by the organism themselves.

Fully functional Shikimate pathway. The enzyme EPSP-synthase is needed
in order to form the three essential aromatic amino acids Phenylalanine,
Tryptophane and Tyrosine.

Glyphosates ability to inhibit this pathway is the reason why it also classifies as antibiotic, as bacteria are also not able to synthesize the essential amino acids anymore and pass away.

Shikimate pathway interrupted through Glyphosate. Through inhibition
of the EPSP Synthase with Glyphosate the amino acids can’t be generated
anymore.