Angewandte Chemie International Edition · 2016 · 158 citations · 20 references
PharmacyBioengineeringBiotechnologyIndustrial BiotechnologyMetabolic EngineeringSynthetic BiologyCombinatorial BiosynthesisCombinatorial SynthesisDiversity-oriented SynthesisMetabolic Pathway EngineeringSteroid BiosynthesisTerpenoid BiosynthesisDiterpene BiosynthesisMicrobial Production Of TerpenoidsMonoterpene BiosynthesisScalable ProductionTerpene Metabolic EngineeringTerpene SynthasesTerpenoid Biosynthesis EngineeringType Ii Polyketide Synthases
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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