Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis |
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| Authors: | Dr Johan Andersen‐Ranberg Dr Kenneth Thermann Kongstad Dr Morten Thrane Nielsen Dr Niels Bjerg Jensen Dr Irini Pateraki Dr Søren Spanner Bach Britta Hamberger Prof Dr Philipp Zerbe Prof Dr Dan Staerk Prof Dr Jörg Bohlmann Prof Dr Birger Lindberg Møller Prof Dr Björn Hamberger |
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| Institution: | 1. Department of Plant and Environmental Sciences, Center for Synthetic Biology, K?benhavn, Denmark;2. Natural Products Research, University of Copenhagen, Denmark;3. Evolva AS, K?benhavn, Denmark;4. Department of Plant Biology, University of California Davis, USA;5. Michael Smith Laboratories, University of British Columbia, Vancouver, Canada |
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| Abstract: | Plant‐derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are “new‐to‐nature”. Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae. |
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| Keywords: | biosynthesis biocatalysis combinatorial biosynthesis cyclizations terpenes |
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