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Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
Author(s) -
AndersenRanberg Johan,
Kongstad Kenneth Thermann,
Nielsen Morten Thrane,
Jensen Niels Bjerg,
Pateraki Irini,
Bach Søren Spanner,
Hamberger Britta,
Zerbe Philipp,
Staerk Dan,
Bohlmann Jörg,
Møller Birger Lindberg,
Hamberger Björn
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201510650
Subject(s) - diterpene , biosynthesis , enantiomer , chemistry , stereochemistry , diastereomer , stereoselectivity , modularity (biology) , computational biology , enzyme , biology , biochemistry , evolutionary biology , catalysis
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 .