Changing Face: A Key Residue for the Addition of Water by Sclareol Synthase

Meirong Jia, Terrence E. O'Brien, Yue Zhang, Justin Siegel, Dean J. Tantillo, Reuben J. Peters

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Sclareol synthase from Salvia sclarea (SsSS) naturally acts on 8α-hydroxy-copalyl diphosphate (1), stereoselectively adding water to produce (13R)-sclareol (2a), and similarly yields hydroxylated products with many-fold other such bicyclic diterpene precursors. Here, a key residue for this addition of water was identified. Strikingly, substitution with glutamine switches stereochemical outcome with 1, leading to the selective production of (13S)-sclareol (2b). Moreover, changes to the stereospecificity of water addition with the structurally closely related substrate copalyl diphosphate (4) could be accomplished with alternative substitutions. Thus, this approach is expected to provide biosynthetic access to both epimers of 13-hydroxylated derivatives of many-fold labdane-related diterpenes.

Original languageEnglish (US)
Pages (from-to)3133-3137
Number of pages5
JournalACS Catalysis
Volume8
Issue number4
DOIs
StatePublished - Apr 6 2018

Fingerprint

Diterpenes
Water
Substitution reactions
Glutamine
Switches
Derivatives
Substrates
sclareol
copalyl diphosphate
labdane

ASJC Scopus subject areas

  • Catalysis

Cite this

Jia, M., O'Brien, T. E., Zhang, Y., Siegel, J., Tantillo, D. J., & Peters, R. J. (2018). Changing Face: A Key Residue for the Addition of Water by Sclareol Synthase. ACS Catalysis, 8(4), 3133-3137. https://doi.org/10.1021/acscatal.8b00121

Changing Face : A Key Residue for the Addition of Water by Sclareol Synthase. / Jia, Meirong; O'Brien, Terrence E.; Zhang, Yue; Siegel, Justin; Tantillo, Dean J.; Peters, Reuben J.

In: ACS Catalysis, Vol. 8, No. 4, 06.04.2018, p. 3133-3137.

Research output: Contribution to journalArticle

Jia, M, O'Brien, TE, Zhang, Y, Siegel, J, Tantillo, DJ & Peters, RJ 2018, 'Changing Face: A Key Residue for the Addition of Water by Sclareol Synthase', ACS Catalysis, vol. 8, no. 4, pp. 3133-3137. https://doi.org/10.1021/acscatal.8b00121
Jia, Meirong ; O'Brien, Terrence E. ; Zhang, Yue ; Siegel, Justin ; Tantillo, Dean J. ; Peters, Reuben J. / Changing Face : A Key Residue for the Addition of Water by Sclareol Synthase. In: ACS Catalysis. 2018 ; Vol. 8, No. 4. pp. 3133-3137.
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