Diterpene Synthase-Catalyzed Biosynthesis of Distinct Clerodane Stereoisomers

Pelot, Kyle A.; Hagelthorn, David M.; Hong, Young J.; Tantillo, Dean J.; Zerbe, Philipp

doi:10.1002/cbic.201800580

Diterpene Synthase-Catalyzed Biosynthesis of Distinct Clerodane Stereoisomers

Journal Article · Tue Nov 13 00:00:00 EST 2018 · ChemBioChem: a European journal of chemical biology

DOI:https://doi.org/10.1002/cbic.201800580· OSTI ID:1633651

Pelot, Kyle A. ^[1]; Hagelthorn, David M. ^[2]; Hong, Young J. ^[3]; Tantillo, Dean J. ^[3]; ^[2]

Univ. of California, Davis, CA (United States). Dept. of Plant Biology; UC Davis
Univ. of California, Davis, CA (United States). Dept. of Plant Biology
Univ. of California, Davis, CA (United States). Dept. of Chemistry

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.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of California, Davis, CA (United States)

Sponsoring Organization:: DOE Joint Genome Institute Community Science Program; NSF Graduate Research Fellowship Program; USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23). Biological Systems Science Division

Grant/Contract Number:: SC0019178

OSTI ID:: 1633651

Alternate ID(s):: OSTI ID: 1613140
OSTI ID: 1483731

Journal Information:: ChemBioChem: a European journal of chemical biology, Journal Name: ChemBioChem: a European journal of chemical biology Journal Issue: 1 Vol. 20; ISSN 1439-4227

Publisher:: ChemPubSoc EuropeCopyright Statement

Country of Publication:: United States

Language:: English

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