title: Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.
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.
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Andersen-Ranberg
authors.affiliation: Natural Products Research, University of Copenhagen, Denmark.
authors.forename: Kenneth Thermann
authors.initials: KT
authors.lastname: Kongstad
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.
authors.forename: Morten Thrane
authors.initials: MT
authors.lastname: Nielsen
authors.affiliation: Evolva AS, København, Denmark.
authors.forename: Niels Bjerg
authors.initials: NB
authors.lastname: Jensen
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.
authors.forename: Irini
authors.initials: I
authors.lastname: Pateraki
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.
authors.forename: Søren Spanner
authors.initials: SS
authors.lastname: Bach
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.
authors.forename: Britta
authors.initials: B
authors.lastname: Hamberger
authors.affiliation: Department of Plant Biology, University of California Davis, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zerbe
authors.affiliation: Natural Products Research, University of Copenhagen, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Staerk
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bohlmann
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.
authors.forename: Birger Lindberg
authors.initials: BL
authors.lastname: Møller
authors.affiliation: Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark. bjoernh@plen.ku.dk.
authors.forename: Björn
authors.identifier: http://orcid.org/0000-0003-1249-1807
authors.initials: B
authors.lastname: Hamberger
mesh_terms: D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D004224:Diterpenes
keywords: biocatalysis; biosynthesis; combinatorial biosynthesis; cyclizations; terpenes