Journal
METABOLIC ENGINEERING
Volume 19, Issue -, Pages 33-41Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2013.05.004
Keywords
Limonene; Perillyl alcohol; Mevalonate pathway; Microbial production; Metabolic engineering; Escherichia coli
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Funding
- U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research [DE-AC02-05CH11231]
- Fundacion Ramon Areces
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Limonene is a valuable monoterpene used in the production of several commodity chemicals and medicinal compounds. Among them, perillyl alcohol (FOR) 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 FOR. 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 FOR. Further metabolic engineering of the pathway and in situ product recovery using anion exchange resins would make this engineered E. cob a potential production platform for any valuable limonene derivative. (C) 2013 Elsevier Inc. All rights reserved.
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