12 January 2016

PUBLICATION: Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis

J. Andersen-Ranberg, KT Kongstad, MT Nielsen, NB Jensen, I Pateraki, SS Bach, B Hamberger, P Zerbe, D Stærk, J Bohlmann, BL Møller, BR Hamberger: Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis. Angewandte Chemie 10.1002/anie.201510650 (2016)

The modular nature of diterpene 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.

Combinatorial wheel

click figure to enlarge

Link to full article + extensive supporting material here https://onlinelibrary.wiley.com/doi/10.1002/ange.201510650/full