How Roundup® Works

This week's molecule is N-(phosphonomethyl) glycine better known as glyphosate, the active ingredient in the herbicide Roundup® [Monday's Molecule #17]. Glycophosate is a potent inhibitor of one of the key enzymes in the pathway for synthesis of the aromatic amino acids, tryptophan, phenylalanine, and tyrosine [How Cells Make Tryptophan, Phenyalanine, and Tyrosine].

Specifically, the herbicide blocks the activity of EPSP synthase, the enzyme that catalyzes one of the steps leading to chorismate. Chorismate is the precursor of all three aromatic amino acids so by blocking this enzyme, the synthesis of three plant amino acids is prevented.


Plants need to synthesize all 20 amino acids so this blockage causes plants to die. The glyphosate mechanism is well known from studies of the homologous bacterial versions of EPSP synthase. An example of glyphosate bound to the active site of the E. coli enzyme is shown on the right. When glyphosate is bound, the enzyme is incapable of catalyzing any reaction.

As pointed out earlier in "How Cells Make Tryptophan, Phenyalanine, and Tyrosine," animals have lost the ability to synthesize chorismate and the aromatic amino acids. They require tryptophan, phenyalanine, and tyrosine in their diet. What this means is that the potent herbicide, glyphosate, has no effect on animals since they have already dispensed with the EPSP synthase enzyme. That's one of the reasons why Roundup® is so safe for humans.

Those of you who have used Roundup® on your driveways and walkways know that it kills all plants indiscriminately. You'd better not get it on your wife's favorite roses (... not that I'm admitting anything, mind you).

You can't spray it on crops, such as soybeans, corn, cotton, granola, and wheat to get rid of weeds because it kills the crops as well as the weeds. Wouldn't it be nice to have Roundup® resistant crops so you could spray them to control weeds?

Monsanto makes Roundup® and and they thought so too. Now, how do you genetically modify plants to make them resistant?