Catalytic Bases and Stereocontrol in Lamiaceae Class II Diterpene Cyclases

dc.contributor.author Schulte, Samuel
dc.contributor.author Potter, Kevin
dc.contributor.author Peters, Reuben
dc.contributor.author Lemke, Cody
dc.contributor.author Peters, Reuben
dc.contributor.department Biochemistry, Biophysics and Molecular Biology
dc.date 2020-04-01T21:24:37.000
dc.date.accessioned 2020-06-29T23:46:53Z
dc.date.available 2020-06-29T23:46:53Z
dc.date.copyright Mon Jan 01 00:00:00 UTC 2018
dc.date.issued 2018-06-26
dc.description.abstract <p>Plants from the widespread Lamiaceae family produce many labdane-related diterpenoids, a number of which serve medicinal roles, and whose biosynthesis is initiated by class II diterpene cyclases (DTCs). These enzymes utilize a general acid-base catalyzed cyclo-isomerization reaction to produce various stereoisomers of the eponymous labdaenyl carbocation intermediate, which can then undergo rearrangement and/or the addition of water prior to terminating deprotonation. Identification of the pair of residues that cooperatively serve as the catalytic base in the DTCs that produce ent-copalyl diphosphate (CPP) required for gibberellin phytohormone biosynthesis in all vascular plants has led to insight into the addition of water as well as rearrangement. Lamiaceae plants generally contain an additional DTC that produces the enantiomeric normal CPP, as well as others that yield hydroxylated products derived from the addition of water. Here the catalytic base in these DTCs was investigated. Notably, changing two adjacent residues that seem to serve as the catalytic base in the normal CPP synthase from Salvia miltiorrhiza (SmCPS) to the residues found in the closely related perigrinol diphosphate synthase from Marrubium vulgare (MvPPS), which produces a partially rearranged and hydroxylated product derived from the distinct syn stereoisomer of labdaenyl+, altered product outcome in an unexpected fashion. Specifically, the relevant SmCPS:H315N/T316V double mutant produces terpentedienyl diphosphate, which is derived from complete substituent rearrangement of syn rather than normal labdaenyl+. Accordingly, alteration of the residues that normally serve as the catalytic base surprisingly can impact stereo-control.</p>
dc.description.comments <p>This is a manuscript of an article published as Schulte, Samuel, Kevin C. Potter, Cody Lemke, and Reuben J. Peters. "Catalytic bases and stereocontrol in Lamiaceae class II diterpene cyclases." <em>Biochemistry</em> 57, no. 25 (2018): 3473-3479. doi: <a href="https://doi.org/10.1021/acs.biochem.8b00193" title="DOI URL">10.1021/acs.biochem.8b00193</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/bbmb_ag_pubs/266/
dc.identifier.articleid 1277
dc.identifier.contextkey 17171036
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bbmb_ag_pubs/266
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/10738
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/bbmb_ag_pubs/266/2018_Peters_CatalyticBasesManuscript.pdf|||Fri Jan 14 23:03:36 UTC 2022
dc.source.uri 10.1021/acs.biochem.8b00193
dc.subject.disciplines Biochemistry
dc.subject.disciplines Biophysics
dc.subject.disciplines Molecular Biology
dc.subject.disciplines Plant Sciences
dc.subject.disciplines Structural Biology
dc.title Catalytic Bases and Stereocontrol in Lamiaceae Class II Diterpene Cyclases
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 498a24ec-81d7-4bee-b145-323d38e7a392
relation.isOrgUnitOfPublication c70f85ae-e0cd-4dce-96b5-4388aac08b3f
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