Annual report

IUCRP UC Discovery Gr
ant success story
UC Discovery Gr
Fighting Malaria:
Creating cheap, simple microbial drug factories
Worldwide, nearly two million people die of
this same drug production method can be used malaria every year. Unfortunately, the most widely to manufacture many other compounds from available, affordable anti-malarial drugs are based the isoprenoid family, including terpene-based on chloroquine, and the Plasmodium parasite that fragrances and flavors. Steve del Cardayre is causes malaria has developed resistance to it. Product Manager-Fermentation at Codexis the Drugs based on an ancient Chinese extract of the spinoff of Maxygen that is pursuing the research plant Sweet Wormwood, or Artemisia annua, are with Keasling. He says that the UC Discovery more effective, but they are too expensive for Grant gave the company a valuable opportunity to undertake exploratory and fairly high risk research and validate their approach to producing these value-added products. According to del Cardayre, the product lines “looked good on paper” but the science was at such an early stage it was not possible for the firm to make an informed decision about investing in an all-out R&D program.
Keasling’s work showed that the science works but alerted Codexis to the substantial additional investment required to actually develop and commercialize fragrance and flavor products. They decided not to pursue in-house development of the products and redirected their efforts to marketing the tools developed in their research Dr. Jay Keasling
partnership with Keasling as part of their gen, a California-based biotechnology company, have come up with a way to do just that. Through Del Cardayre emphasizes that the UC Discovery a research partnership funded by a UC Discovery Grant gave them a valuable opportunity to Grant, Keasling and Maxygen modified the bacteri- undertake the exploratory research that both um Escherichia coli to produce complex chemicals validated the approach and showed the expense with medicinal qualities. The bacterium can now to be prohibitive. It saved them from making produce amorphadiene, a precursor to the anti- substantial investment in something that malaria drug artemisinin — the active ingredient in ultimately would prove to expensive to pursue. Sweet Wormwood extracts— and the most difficult In addition to substantial cost savings that freed up internal R&D resources for other strategic targetes, the project added a new technology to To produce amorphadiene in E. coli, Keasling and his research team inserted a combination of genes from E. coli, yeast, and Sweet Wormwood into the host bacterium to construct an entirely new metabolic pathway. The modified bacterium now converts inexpensive sugars into large quantities of amorphadiene. By cloning one or two more genes Industry Sponsor: Maxygen, Inc. (later acquired by Codexis, Inc.) from Sweet Wormwood, it will be possible to produce large quantities of artemisinin inexpensively. Prof. Jay Keasling, Chemical Engineering, UC Berkeley Title: Metabolic Engineering of Microorganisms for Sesquiterpene What’s in it for the California economy? Well, Grant #: (Bio99-10044) Grant Period: 9/1/2000-8/31/2002 Grant #: (biostar 01-10223) Grant Period: 8/13/2002-8/12/2003 ���� ����� ���������� � �������� �������������������

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