Engineering Escherichia coli for production of functionalized terpenoids using plant P450s

被引:269
作者
Chang, Michelle C. Y.
Eachus, Rachel A.
Trieu, William
Ro, Dae-Kyun
Keasling, Jay D. [1 ]
机构
[1] Univ Calif Berkeley, Calif Inst Quantitat Biomed Res, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Chem Engn, Dept Bioengn, Berkeley, CA 94720 USA
[3] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA
关键词
D O I
10.1038/nchembio875
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Terpenoids are a highly diverse class of natural products that have historically provided a rich source for discovery of pharmacologically active small molecules(1), 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.
引用
收藏
页码:274 / 277
页数:4
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