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Chembiochem. 2019 Jan 2;20(1):111-117. doi: 10.1002/cbic.201800580. Epub 2018 Nov 28.

Diterpene Synthase-Catalyzed Biosynthesis of Distinct Clerodane Stereoisomers.

Author information

1
Department of Plant Biology, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA.
2
Department of Chemistry, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA.

Abstract

The diterpene synthase clerodienyl diphosphate synthase 1 (PvCPS1) from the crop plant switchgrass (Panicum virgatum) stereoselectively converts (E,E,E)-geranylgeranyl diphosphate (GGPP) into the clerodane natural product, cis-trans-clerodienyl diphosphate (CLPP, 1). Structure-guided point mutations of PvCPS1 redirected product stereoselectivity toward the formation of a rare cis-clerodane diastereomer, cis-cis-CLPP (2). Additionally, an alternative cis-clerodane diastereomer, (5S,8S,9R,10R)-13Z-CLPP (3), was produced when treating PvCPS1 and select variants thereof with the cis-prenyl substrate (Z,Z,Z)-nerylneryl diphosphate (NNPP). These results support the hypothesis that substrate configuration and minor active-site alterations impact precatalysis substrate folding in the stereoselective biosynthesis of clerodane diterpenoid scaffolds, and can be employed to provide enzymatic access to a broader range of bioactive clerodane natural products.

KEYWORDS:

clerodane diterpenes; diterpene synthase; plant natural products; protein mutagenesis; terpenoid metabolism

PMID:
30393911
DOI:
10.1002/cbic.201800580

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