Expanding the landscape of diterpene structural diversity by stereochemically controlled combinatorial biosynthesis

Johan Andersen-Ranberg, Kenneth Thermann Kongstad, Morten Thrane Nielsen, Niels Bjerg Jensen, Irini Pateraki, Søren Spanner Bach, Britta Hamberger, Philipp Zerbe, Dan Stærk, Jörg Bohlmann, Birger Lindberg Møller, Björn Robert Hamberger

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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.

OriginalsprogEngelsk
TidsskriftAngewandte Chemie International Edition
Vol/bind55
Udgave nummer6
Sider (fra-til)2142-2146
Antal sider5
ISSN1433-7851
DOI
StatusUdgivet - 5 feb. 2016

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