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Article
Nature Biotechnology  21, 796 - 802 (2003)
Published online: 1 June 2003; | doi:10.1038/nbt833

Engineering a mevalonate pathway in Escherichia coli for production of terpenoids

Vincent J J Martin1, 2, 3, Douglas J Pitera1, 3, Sydnor T Withers1, Jack D Newman1 & Jay D Keasling1

1  Department of Chemical Engineering, 201 Gilman Hall, University of California, Berkeley, California 94720-1462, USA.

2  Lawrence Berkeley National Laboratory, 1 Cyclotron Road (HILD 201), Berkeley, California 94720, USA.

3  These authors contributed equally to this work.

Correspondence should be addressed to Jay D Keasling keasling@socrates.berkeley.edu
Isoprenoids are the most numerous and structurally diverse family of natural products. Terpenoids, a class of isoprenoids often isolated from plants, are used as commercial flavor and fragrance compounds and antimalarial or anticancer drugs. Because plant tissue extractions typically yield low terpenoid concentrations, we sought an alternative method to produce high-value terpenoid compounds, such as the antimalarial drug artemisinin, in a microbial host. We engineered the expression of a synthetic amorpha-4,11-diene synthase gene and the mevalonate isoprenoid pathway from Saccharomyces cerevisiae in Escherichia coli. Concentrations of amorphadiene, the sesquiterpene olefin precursor to artemisinin, reached 24 mug caryophyllene equivalent/ml. Because isopentenyl and dimethylallyl pyrophosphates are the universal precursors to all isoprenoids, the strains developed in this study can serve as platform hosts for the production of any terpenoid compound for which a terpene synthase gene is available.

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REFERENCE
Terpenoids: Higher
Nature Encyclopaedia of Life Sciences

REVIEWS
Timeline: Metabolic engineering for drug discovery and development
Nature Reviews Drug Discovery Perspective (01 Dec 2003)
Tropical infectious diseases: Metabolic maps and functions of the Plasmodium falciparum apicoplast
Nature Reviews Microbiology Review (01 Mar 2004)

RESEARCH
Structure of 4-diphosphocytidyl-2-C- methylerythritol synthetase involved in mevalonate- independent isoprenoid biosynthesis
Nature Structural Biology Article (01 Jul 2001)

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Nature Biotechnology
ISSN: 1087-0156
EISSN: 1546-1696
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