Engineering Escherichia coli for production of functionalized terpenoids using plant P450s
Abstract
Terpenoids are a highly diverse class of natural products that have historically provided a rich source for discovery of pharmacologically active small molecules, 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.
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Investigators have concentrated on expressing enzymes from phases 1 and 2 of the artemisinin biosynthetic route in transgenic organisms, including HMGR, FPPS, ADS, and CYP71AV1.
“To date, investigators have concentrated on expressing the enzymes from phases 1 and 2 of the biosynthetic route to artemisinin in transgenic organisms (see Scheme 9 in Section 3). These have included: HMG-CoA reductase (HMGR) [370]; farnesyl diphosphate synthase (FPPS) [371, 372,373,374]; amorpha-4,11-diene synthase (ADS) [375,376,377]; and the P450 enzyme which oxidises amorpha-4,11-diene to art”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [377]
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- Authors
- Chang, M. C. Y., Eachus, R. A., Trieu, W., Ro, D.-K., & Keasling, J. D.
- Affiliations
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Keasling, Jay D
- Venue
- Nature Chemical Biology
- Published
- 2007-04-15
- Volume
- 3
- Issue
- 5
- Pages
- 274-277
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2014177423
- Cited by
- 364
- References
- 33
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 19 · 2020: 21 · 2019: 21 · 2018: 16 · 2017: 21 · 2016: 18 · 2015: 29 · 2014: 18 · 2013: 29 · 2012: 25
- FWCI
- 10.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Keywords
- terpenoids, cytochrome P450, Escherichia coli, heterologous biosynthesis, in vivo oxidation, metabolic engineering, microbial production of natural products, paclitaxel, artemisinin
- MeSH terms
- Cytochrome P-450 Enzyme System, Escherichia coli, Plants, Terpenes, Protein Engineering, Molecular Structure, Artemisinins
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