Skip to comments.Yeast to make malaria drug on demand
Posted on 04/12/2013 1:04:04 AM PDT by neverdem
A natural biochemical pathway that produces the antimalarial drug artemisinin in the sweet wormwood plant has been fully reconstructed in yeast. The engineered yeast cells churn out high concentrations of a precursor that can be converted in a few steps into the first-line malaria drug. According to the team behind the advance, their semi-synthetic route should help smooth out seasonal variations in supply.
Semi-synthetic artemisinin has been in the pipeline since 2006, when Jay Keaslings group at the Lawrence Berkeley National Laboratory in California, US, reported rewriting the genome of ordinary brewers yeast to encourage it to make artemisinic acid.1 But piecing together a practical route for making the drug precursor in yeast and then transforming it into the finished product has proved tricky. It has remained cheaper and more straightforward to extract the drug from its natural source.
Artemisinic acid produced by the yeast can be easily turned into artemisinin by chemical synthesisThe new study2, led by researchers at US biotech company Amyris in Emeryville, California, describes how the team solved an annoying problem with their yeast-based production plan genes for two particular biosynthetic enzymes were making the yeast ill. The yeast became very sick when these genes were expressed so we had to figure out why, says Chris Paddon, principal scientist at Amyris. Another gene that we discovered led to healthy, happy yeast but they didnt produce a lot of artemisinic acid.
The breakthrough came with the discovery of two more sweet wormwood genes encoding dehydrogenase enzymes. With the full complement of five key enzymes, the yeast produced artemisinic acid at concentrations more than ten times what had been achieved before. To solubilise the molecule, which the yeast originally produced as a crystalline precipitate, they grew the cells in isopropyl myristate oil.
Paul ONeill, a synthetic organic chemist at the University of Liverpool, UK, says its the genetic aspects of the work that make it so striking. They do some semi-synthetic optimisation but what I would say is impressive is the engineering of the yeast. The synthetic organic chemistry required in the next stage, to transform artemisinic acid into artemisinin, is drawn from existing literature, he notes.
According to Amyris cofounder Jack Newman, industry partner Sanofi is already in the process of making 35 metric tons of semi-synthetic artemisinin roughly equivalent to 70 million malaria cures although using a slightly different process. The yeast strain that is outlined in the paper is exactly whats going into the scale-up. The chemistry was a lot of innovation from Sanofi but they havent published it yet, he says.
With the commercial launch of the process imminent, Kelly Chibale, a medicinal chemist at the University of Cape Town, South Africa, says it remains to be seen whether the kind of yields demonstrated at bench scale can be matched commercially.
As the World Health Organization-recommended first-line treatment for malaria, artemisinin is currently the most important compound available for treating the disease. However, there are more potent antimalarials, including the artemisinin-inspired molecule OZ439, in the pipeline. Despite borrowing its peroxide warhead from artemisinin, OZ439 is fully synthetic. Its a very beautiful example of how nature can provide inspiration for wholly synthetic versions, says Chibale. Whats remarkable is that it was designed to produce a single dose oral cure in humans and it has outstanding antimalarial and stability properties that artemisinins dont have.
Paddon and Newman argue their semi-synthetic route will help keep the price of artemisinin stable by uncoupling the production process from all of the vagaries of agricultural production and a 14-month crop cycle. So why not make a fully synthetic compound instead? If youve got something thats synthetic that you can make in four or five steps its always going to be cheaper, says ONeill. But I would say for the immediate future the three to five year scenario we will continue to use the semi-synthetics.
PTL! Artemesin is a great med for malaria. It works very quickly and the sufferer often feels better in a matter of 6 hours or even less. It has very few side effects, too.
Once again, beer, or brewers yeast in this case, saves lives.
I have been contemplating making a brew from marquissa juice, in the states marquissa is called passion fruit. It takes similar to a peach and is just heavenly. I haven’t quite gotten the nerve to try and I don’t as yet have brewers yeast. At present we don’t know if we’ll be in this house for more than a month or so and so would be disturbing the brew anyway.
I’ve thought about you thinking you would have some ideas.
Well then, once we get our longer-term housing sorted out, I may just give it a try.
Also, brewer’s yeast is often available at, of all places, health food stores, as a food supplement.
Or someone could trade a big jar for some Papua New Guinea coffee...
Thanks for the ping!
You’re Welcome, Alamo-Girl!