Abstract
The total biosynthesis of (-)-terpestacin was achieved by heterologous expression of four biosynthetic enzyme genes ( tpcA- D) in Aspergillus oryzae. After construction of preterpestacin I by the action of bifunctional terpene synthase (TpcA), two cytochrome P450s (TpcBC) activate inert C-H bond to install three hydroxyl groups on the A-ring in stereo- and regioselective manners. Subsequently, a flavin-dependent oxidase (TpcD) catalyzes oxidation of the vicinal diol moiety to give a α-diketone, which undergoes an enolization to furnish terpestacin. The successful synthesis of structurally elaborated terpestacin showed that a reconstitution approach that harnesses several biosynthetic enzyme genes in A. oryzae could be a promising alternative to the current chemical synthesis of natural terpenoids.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkyl and Aryl Transferases / genetics
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Alkyl and Aryl Transferases / metabolism
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Angiogenesis Inhibitors / biosynthesis*
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Angiogenesis Inhibitors / chemistry
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Aspergillus oryzae / enzymology
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Aspergillus oryzae / genetics
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Aspergillus oryzae / metabolism*
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Bridged Bicyclo Compounds / chemistry
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Bridged Bicyclo Compounds / metabolism
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Catalysis
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism
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Genes, Fungal
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Magnetic Resonance Spectroscopy / methods
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Mass Spectrometry / methods
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Molecular Structure
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Oxidoreductases / genetics
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Oxidoreductases / metabolism
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Stereoisomerism
Substances
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Angiogenesis Inhibitors
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Bridged Bicyclo Compounds
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terpestacin
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Cytochrome P-450 Enzyme System
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Oxidoreductases
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Alkyl and Aryl Transferases
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terpene synthase