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Tuesday, March 13, 2007

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?


Steve Reuland said...

"Now, how do you genetically modify plants to make them resistant?"

Well let's see. If it's me, I take the ESPS enzyme and apply directed evolution to change its active site such that it still synthesizes chorismate, but no longer binds glyphosate. Of course it's already been done by these guys.

Another way to do it is to introduce an enzyme that efficiently detoxifies glyphosate. These guys found one and then improved it through directed evolution.

I suspect another way to do it would be simply to add multiple copies of the ESPS gene so that the enzyme was overproduced, and therefore wasn't saturated by glyphosate.

The way that Monsanto actually did it though (I think) is that they found an ESPS gene that's tolerant to glyphosate in some other organism and they stuck it into their plants.

Larry Moran said...

It was a rhetorical question, designed to lead into my next article to be published tomorrow.

Thanks anyway. At least you didn't reveal the way it was actually done by Monsanto scientists.

Nick (Matzke) said...

Whatever Monsanto did, apparently Mother Nature did by itself. See this article on roundup-resistant cocaine plants in Columbia:

Nick (Matzke) said...

Er, try this link.

Larry Moran said...

I'm going to cover the mechanisms of Roundup resistance on Thursday. Please be patient.

Anonymous said...

I wouldn't put much stock in that Wired report on resistant coca. I think it may one day appear on this blog as an urban myth. Coca is actually very difficult to get permission to work with in North America and very difficult to get to grow well in culture (necessary for transformation unfortunately). It is very unlikely south American drug lords have the research resources to produce it, but stranger things have apparently happened.

By the way, it's EPSP synthase, not ESPS, but we know what you meant.

Greg Laden said...

Does this mean I can drink roundup?

NickM said...

It is very unlikely south American drug lords have the research resources to produce it, but stranger things have apparently happened.

That's the point, it was random mutation and (unnatural selection). The selection part is the U.S. government flying around Columbia spraying coca fields with roundup.

Anonymous said...

As far as DESTROYING areas in South America that grow COCA PLANTS : when the US is busy flying over, dispensing Round-Up , they should ALSO be dropping an AMPLE SUPPLY of KUDZU SEEDS ! Then those SOBs that want to work in the Jungle will REALLY have some work to do ! IMAGINE ; a vining, climbing plant that grows up to SIXTY FEET in just a few months of tropical weather ! Those Drug-Growing Regions will be TOTALLY over-grown in just a few years ! Then those Bast$%^'s will have some REAL WORK to do ! YEA !

gil epis said...

In what other human proteins is glyphosate bound?

Anonymous said...

Will roundup eventually kill trees if it is sprayed at the base for extended periods to kill weeds.