title: Engineering a mevalonate pathway in Escherichia coli for production of terpenoids.
abstract: 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 microg 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.
authors.affiliation: Department of Chemical Engineering, 201 Gilman Hall, University of California, Berkeley, California 94720-1462, USA.
authors.forename: Vincent J J
authors.initials: VJ
authors.lastname: Martin
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Pitera
authors.forename: Sydnor T
authors.initials: ST
authors.lastname: Withers
authors.forename: Jack D
authors.initials: JD
authors.lastname: Newman
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D000475:Alkenes / Q000378:metabolism*; D002455:Cell Division; D004734:Energy Metabolism / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods*; D008798:Mevalonic Acid / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods; D013729:Terpenes / Q000378:metabolism*
chemical_list: D000475:Alkenes; D013729:Terpenes; D008798:Mevalonic Acid