Artemisinin made in GM yeast

Successful research now going into development

SUMMARY: Research has created a genetically-modified yeast that can make a key precursor of the leading antimalarial, artemisinin. If process development is successful, this could ease supply shortages and lower prices.

(May 06)

A close precursor of the antimalarial molecule artemisinin - artemisinic acid – has been produced at high concentration from a genetically modified yeast, making it possible, in principle, to “brew” the molecule, according to a recent paper in Nature.

The non-profit company The Institute for OneWorld Health [see RealHealthNews 2, 2005 pp 2-3] is taking the research into development, with the hope of producing artemisinin in bulk more cheaply than from its current source – plantations of the herb sweet wormwood (Artemisia annua).

The Drugs for Neglected Diseases initiative has been aiming to produce a combination at US$1.60 [RealHealthNews 2, 2005 pp 4-5], but the great goal would be to reduce WHO’s recommended artemisinin combination therapies to a price affordable by rural African mothers, who currently pay some 10 US cents for over-the-counter, but now ineffective, chloroquine.

Swedish researchers had created a chemically earlier precursor, amorpha-4-11-diene, by cloning an Artemisia annua gene into the yeast Saccharomyces cerevisiae, but the latest work by scientists at the California Institute of Quantitative Biomedical Research of the Lawrence Berkeley National Laboratory, in collaboration with Amyris Biotechnologies, went further.

The California trick was to clone in further genes creating a whole metabolic (chemical) pathway in Artemisia annua that “oxidises” amorpha-4-11-diene in three steps to artemisinic acid.

“This achievement is an early proof of concept that the biosynthetic manufacturing strategy can be achieved at the laboratory scale” commented OneWorld Health. “However, several challenges remain as the yield of artemisinic acid would need to be improved several hundred fold to be economically acceptable for large-scale manufacturing.”

"The team at UC Berkeley and Amyris have done a great job moving this important project forward," said Victoria Hale, founder and CEO of OneWorld Health. "We still have a long way to go, but this puts us one step closer to a low-cost treatment for malaria."

Supported by a US$43 million grant from the Bill and Melinda Gates Foundation in 2004 to create a unique three-way partnership between the Institute for OneWorld Health, UC Berkeley and Amyris Biotechnologies, OneWorld Health, as the product development partner, will also develop a commercialization strategy “based on a thorough understanding of the worldwide regulatory requirements and an analysis of the current ACT manufacturing supply-chain and distribution models”. - RW

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