Talk:CH391L/S12/Artemisinic Acid Engineering
- Jeffrey E. Barrick 12:41, 15 April 2012 (EDT):History of the compound is very interesting and well done. It might be good to give a short background or link to how malaria works. What kind of organism is Plasmodium? How does an infection progress?
- Peter Otoupal 11:48, 16 April 2012 (EDT) Thanks! I added a brief answer to this in the beginning. Luckily, malaria is a relatively well characterized disease that seems to be receding; the new paper I referenced mentions that malaria cases in Africa have been reduced by 30% in less than 10 years.
- Jeffrey E. Barrick 12:41, 15 April 2012 (EDT):Great description of their work. There is an earlier paper published about a checkpoint in their engineering efforts where they appear to have been moving the yeast enzymes to E. coli to get it to produce artemisinin. Is this evidence that they were evaluating multiple chassis and had to switch to yeast later?.
- Peter Otoupal 14:21, 16 April 2012 (EDT)This article definitely indicates that the Keasling lab was searching for a way to engineer the mevalonate pathway to produce artemsinin for a quite a while. I'm not necessarily an expert at interpreting intent from scientific writing, but it seems to me that there referral to E. coli as a "platform host" for the production of terpenoids suggests that they were only using E. coli as a proof-of-concept chassis. One figure indicates that high concentrations of mevalonate is harmful to E-coli. While they were able to somewhat circumvent this problem, the "maximum yield was not attained" which they attribute to unknown bottlenecks in the pathway. They probably tried more experiments with E. coli optimization, but couldn't surpass these bottlenecks and didn't publish any data about it. They therefore couldn't achieve the high concentrations of mevaolanate that they eventually were able to achieve with S. Cerevisiae, which I guess is the main reason they had to switch. Later in the discussion they also mention that the amorphadiene synthase gene is poorly expressed in E. coli, which may be another reason they switched.
- Jeffrey E. Barrick 12:18, 15 April 2012 (EDT):Looks like you have the new reports of resistance to Artemisinin covered. Do they know what the mutations are and why they make it resistant?
- Peter Otoupal 12:07, 16 April 2012 (EDT)It sounds like the authors are not entirely sure what the exact mutations are and how they provide resistance. They countinually mention a "93-locus genotype" that increases the time it takes to kill the malaria parasite, but I honestly don't know what they are referring to. There may be some clarity in this graph which you could derive.
- Jeffrey E. Barrick 12:41, 15 April 2012 (EDT):It's usually good to avoid value judgements, like calling something "famous", in scientific or formal writing.
- Peter Otoupal 11:48, 16 April 2012 (EDT) Removed all the qualitative judgement calls.
- Martin VJ, Pitera DJ, Withers ST, Newman JD, and Keasling JD. . pmid:12778056.