Letter abstract
Nature Chemical Biology 3, 274 - 277 (2007)
Published online: 15 April 2007 | doi:10.1038/nchembio875
Engineering Escherichia coli for production of functionalized terpenoids using plant P450s
Michelle C Y Chang1, Rachel A Eachus1, William Trieu1, Dae-Kyun Ro1 & Jay D Keasling1,2,3
Terpenoids are a highly diverse class of natural products that have historically provided a rich source for discovery of pharmacologically active small molecules1, such as paclitaxel (Taxol) and artemisinin. Unfortunately, these secondary metabolites are typically produced in low abundance in their host organism, and their isolation consequently suffers from low yields and high consumption of natural resources. Furthermore, chemical synthesis of terpenoids can also be difficult to scale for industrial production. For these reasons, an attractive alternative strategy is to engineer metabolic pathways for production of pharmaceuticals or their precursors in a microbial host such as Escherichia coli. A key step is developing methods to carry out cytochrome P450 (P450)-based oxidation chemistry in vivo. Toward this goal, we have assembled two heterologous pathways for the biosynthesis of plant-derived terpenoid natural products, and we present the first examples of in vivo production of functionalized terpenoids in E. coli at high titer using native plant P450s.
- California Institute for Quantitative Biomedical Research, University of California, Berkeley, Berkeley, California 94720-3224, USA.
- Department of Chemical Engineering, Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720-1462, USA.
- Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720-3224, USA.
Correspondence to: Jay D Keasling1,2,3 e-mail: keasling@berkeley.edu
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