期刊
METABOLIC ENGINEERING
卷 18, 期 -, 页码 69-77出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2013.04.004
关键词
Coumarin; Scopoletin; Umbelliferone; Plant metabolites; Combinatorial biosynthesis
资金
- College of Engineering, University of Georgia, Athens
- University of Georgia Research Foundation, Inc.,
- American Heart Association [11SDG6960001]
- National Science Foundation of China [20976009, 21176018]
- National High-tech Research and Development Program of China [2009AA02Z202]
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology
Coumarins are plant secondary metabolites that have demonstrated a variety of important therapeutic properties, such as antibacterial, anti-inflammatory, and anti-coagulant effects, as well as anti-cancer and anti-AIDS activities. However, knowledge regarding their biosynthesis is relatively limited even for the simplest coumarin molecule, which serves as the gateway molecule to many pharmaceutically important coumarin derivatives. Here we reported the design and validation of artificial pathways leading to the biosynthesis of plant-specific simple coumarins in bacteria. First, Escherichia coli strains were engineered to convert inexpensive phenylpropanoid acid precursors, 4-coumarate and ferulate to simple coumarins, umbelliferone (4.3 mg/L) and scopoletin (27.8 mg/L), respectively. Furthermore, we assembled the complete artificial pathways in E. coli and achieved de novo biosynthesis of umbelliferone and scopoletin without addition of precursors. This study lays the foundation for microbial production of more diverse coumarin compounds. (C) 2013 Elsevier Inc. All rights reserved.
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