Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production |
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| Institution: | 1. Joint Bioenergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA;2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;3. Department of Bioengineering, University of California, Berkeley, CA 94720, USA;4. Department of Chemical & Biomolecular Engineering, University of California, Berkeley, CA 94720, USA;1. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, People''s Republic of China;2. Division of Applied Life Science (BK21 Plus), PMBBRC, Institute of Agriculture and Life Sciences, Gyeongsang National University, Jinju, Republic of Korea;1. Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, PR China;2. SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China;1. Division of Applied Life Science (BK21 Plus), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea;2. Industrial Biotechnology Research Center, KRIBB, Daejeon 305-806, Republic of Korea;1. Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA;2. Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;3. Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA;4. Chemical and Biological Processes Development Group, Pacific Northwest National Laboratory, Richland, WA 99352, USA;5. School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland;6. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;7. Department of Bioengineering, University of California, Berkeley, CA 94720, USA;8. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA;9. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Denmark;1. Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;2. RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan;3. Department of Life Sciences (Biology), Graduate School of Arts and Science, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan;4. Graduate School and Faculty of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan;5. Japan Science and Technology Agency (JST), CREST, Saitama, Japan |
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| Abstract: | Limonene is a valuable monoterpene used in the production of several commodity chemicals and medicinal compounds. Among them, perillyl alcohol (POH) is a promising anti-cancer agent that can be produced by hydroxylation of limonene. We engineered E. coli with a heterologous mevalonate pathway and limonene synthase for production of limonene followed by coupling with a cytochrome P450, which specifically hydroxylates limonene to produce POH. A strain containing all mevalonate pathway genes in a single plasmid produced limonene at titers over 400 mg/L from glucose, substantially higher than has been achieved in the past. Incorporation of a cytochrome P450 to hydroxylate limonene yielded approximately 100 mg/L of POH. Further metabolic engineering of the pathway and in situ product recovery using anion exchange resins would make this engineered E. coli a potential production platform for any valuable limonene derivative. |
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| Keywords: | Limonene Perillyl alcohol Mevalonate pathway Microbial production Metabolic engineering |
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