Wormwood-Artemisinin, Bacteria

[Polgara]

http://discovermagazine.com/2006/dec/cover

After years of perfecting his biological tool kit, Keasling wanted to find a real-world use for it. In 2002 he learned of the dire need for synthetic artemisinin, a compound derived from the sweet wormwood plant, which is 90 percent effective against the parasite that causes malaria and has few side effects (malaria kills some 3 million people a year). However, extracting the drug from sweet wormwood is a slow and expensive process that drives up the cost to as much as 20 times the price of other antimalarial drugs.

I have a great interest in the Myelin Sheath topic, and a fun interest in wormwood. And then, I found this article re: genetic engineering/wormwood.

I would like information and discussion regarding artemisinin and bacteria.

[Tiktaalik]

The only place I know wormwood from is Lucid (absinthe). Didn't know it was anti-bacterial.

[Polgara]

The only place I know wormwood from is Lucid (absinthe). Didn't know it was anti-bacterial.

lol Apparently it is. That's what I'm wondering.

[SkeptiChick]

The following might be of interest to you: http://en.wikipedia.org/wiki/Artemisinin

No where do I see mention of it being anti-bacterial. In the article you linked, it does discuss that the scientist is attempting to use bacteria to synthesize it.

[Polgara]

The following might be of interest to you: http://en.wikipedia.org/wiki/Artemisinin

No where do I see mention of it being anti-bacterial. In the article you linked, it does discuss that the scientist is attempting to use bacteria to synthesize it.

Tnx. No, bacteria is used in the process. I was bantering in last comment.

I'm more interested on research about it, and validity..

[sanguine]

I work in this field, and on the pathway Jay's been modifying (although not on his compound).

The short version is that plants produce many useful natural compounds, but are expensive as drug sources. Keasling's group has done extensive work over the last decade to "port over" the biosynthetic pathway for the synthesis of amorphadiene into E. coli, allowing high-yield (and thus cost effective) production of this precursor compound in microbial bioreactors. Thus, instead of having to grow up fields full of Artemisia annua (aka "sweet wormwood"), you can culture of a vat full of modified E. coli, harvest the amorphadiene, and convert it to the antimalarial compound artemisinin.

Jay's group put a pretty heroic effort into getting this done. They not only had to port over the appropriate enzymes from the Artemisia plant, they also had to extensively modify the E. coli in other ways, including bringing over a portion of the mevalonate pathway (the pathway that eventually generates cholesterol in us -- if you take cholesterol-lowering drugs, they're targeting this pathway) and modifying many coli enzymes to get the yield up high enough to make the bacterially produced amorphadiene affordable.

So, this is a different wormwood from the absinthe kind, and it's not being used as an antibacterial, but as a source of genes to make modified bacteria that make a useful drug precursor.

Jay's is one of the more impressive examples of the growing power of metabolic engineering to make incredibly useful compounds cheaply available at will, instead of requiring us to chop down a bunch of (sometimes endangered) plants to get just a little bit at great expense.

[Polgara]

I work in this field, and on the pathway Jay's been modifying (although not on his compound).

The short version is that plants produce many useful natural compounds, but are expensive as drug sources. Keasling's group has done extensive work over the last decade to "port over" the biosynthetic pathway for the synthesis of amorphadiene into E. coli, allowing high-yield (and thus cost effective) production of this precursor compound in microbial bioreactors. Thus, instead of having to grow up fields full of Artemisia annua (aka "sweet wormwood"), you can culture of a vat full of modified E. coli, harvest the amorphadiene, and convert it to the antimalarial compound artemisinin.

Jay's group put a pretty heroic effort into getting this done. They not only had to port over the appropriate enzymes from the Artemisia plant, they also had to extensively modify the E. coli in other ways, including bringing over a portion of the mevalonate pathway (the pathway that eventually generates cholesterol in us -- if you take cholesterol-lowering drugs, they're targeting this pathway) and modifying many coli enzymes to get the yield up high enough to make the bacterially produced amorphadiene affordable.

So, this is a different wormwood from the absinthe kind, and it's not being used as an antibacterial, but as a source of genes to make modified bacteria that make a useful drug precursor.

Jay's is one of the more impressive examples of the growing power of metabolic engineering to make incredibly useful compounds cheaply available at will, instead of requiring us to chop down a bunch of (sometimes endangered) plants to get just a little bit at great expense.


Very kewl. Tnx. That's a large part of what I was looking to narrow down, etc. I knew it was not antibacterial, just that bacteria was involved in the process. -Any further details are welcomed.

[sanguine]

If you're interested in exploring the pathways involved a little bit more, here are some links:

The amorphadiene biosynthesis pathway:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5195

The isoprene biosynthesis pathway that feeds into it:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5123

There are two pathways that feed into isoprene biosynthesis. The mevalonate pathway, which occurs in humans and other mammals, as well as other organisms, is here:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-922

The methylerythritol phosphate pathway, which occurs in bacteria, is here:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=NONMEVIPP-PWY

Plants have both pathways, with the mevalonate pathway occurring in the cells, and the MEP pathway occurring in the chloroplasts (the photosynthetic factories within plant cells).

What the Keasling group did is to genetically modify E. coli to contain the genes required for the amorphadiene biosynthesis pathway (these are plant genes). They then realized that there wasn't enough material flowing out of the inherent MEP pathway of E. coli, so they engineered in part of the mevalonate pathway (taking the genes from baker's yeast). For fun, try opening the MEP and mevalonate pathways in two adjacent windows on your computer, and see how they start from different molecules and use different reactions to produce the same set of final products -- isopentyl diphosphate and methylallyl diphosphate.

If you need a little primer on how to use the website I'm linking to, there are some online videos available here:

http://biocyc.org/webinar.shtml

[Polgara]

If you're interested in exploring the pathways involved a little bit more, here are some links:

The amorphadiene biosynthesis pathway:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5195

The isoprene biosynthesis pathway that feeds into it:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5123

There are two pathways that feed into isoprene biosynthesis. The mevalonate pathway, which occurs in humans and other mammals, as well as other organisms, is here:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-922

The methylerythritol phosphate pathway, which occurs in bacteria, is here:

http://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=NONMEVIPP-PWY

Plants have both pathways, with the mevalonate pathway occurring in the cells, and the MEP pathway occurring in the chloroplasts (the photosynthetic factories within plant cells).

What the Keasling group did is to genetically modify E. coli to contain the genes required for the amorphadiene biosynthesis pathway (these are plant genes). They then realized that there wasn't enough material flowing out of the inherent MEP pathway of E. coli, so they engineered in part of the mevalonate pathway (taking the genes from baker's yeast). For fun, try opening the MEP and mevalonate pathways in two adjacent windows on your computer, and see how they start from different molecules and use different reactions to produce the same set of final products -- isopentyl diphosphate and methylallyl diphosphate.

If you need a little primer on how to use the website I'm linking to, there are some online videos available here:

http://biocyc.org/webinar.shtml

Awesome. I shall peruse and post.