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Bioengineered Yeast Could Increase Supplies of Potent Malaria Drug

Scientists have taken a step that could increase supplies of the potent, but expensive anti-malaria drug artemisinin, now derived from an Asian plant. They have created a strain of yeast that can make a chemical precursor to this drug. The researchers say their advance could generate large amounts of the drug efficiently and cheaply.

Malaria kills more than one million people annually. The parasite is becoming increasingly resistant to older, less expensive drugs, but artemisinin and its derivatives kill it quickly, so they have become the drug of choice for treating resistant strains. The World Health Organization (WHO) recommends that treatment include one of the artemisinin compounds in combination with established drugs.

It is extracted from the sweet wormwood plant in China and Vietnam, but supplies are limited and the compound is expensive, so it is not possible to treat many malaria sufferers in the developing world.

"The reason that the drug is very expensive is because it's produced in minute quantities in the plant, so it takes lot of plant material to get enough drug to treat one patient," said Jay Keasling, a chemical and biological engineer at the University of California at Berkeley.

Mr. Keasling's team has devised a possible way around the artemisinin supply problem. They report in the journal Nature that they engineered a yeast to accept two sweet wormwood genes so that it is capable of churning out large quantities of artemisinic acid, a precursor of artemisinin.

Other researchers have shown that this precursor can be converted into artemisinin in just a few chemical steps.

"By producing it in the microbe, we can produce it in very high yields using a process that we use in the Western world to produce many of our own drugs. It produces in high yields so we don't need a lot of the plants," he added.

Keasling says chemical tests show that the synthetic artemisinin is structurally the same as the natural form. But just to be sure and to comply with government drug regulators, the compound will be tested in animals and humans for its safety and effectiveness against malaria.

"There is no reason why it shouldn't be equivalent. It will, in fact, be easier to purify because it is produced in relatively pure form in the yeast that we have engineered, so it could potentially have fewer contaminants and therefore might even be a better drug than the one that is currently available," he noted.

The researchers hope to have the process optimized and scaled-up in five to 10 years. They say their findings could reduce the cost of the active ingredient in artemisinin by 90 percent and help save lives.

Another synthetic artemisinin approach is further advanced. A compound called RBx-11160 is a slightly altered version of the drug that makes it water soluble for oral consumption or injection. The changes also make it more stable than the natural compound, so less of it is broken down as it travels the bloodstream where the malaria parasite lives. Its simpler structure means it should be much cheaper to produce than the plant version. Tests in mice show that it cures malaria faster. Preliminary human tests in Britain have been promising, and it is about to begin human trials in India, Thailand, and Africa.