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

ABSTRACT: Sclareol synthase from Salvia sclarea (SsSS) naturally acts on 8?-hydroxy-copalyl diphosphate (1), stereoselectively adding water to produce (13R)-sclareol (2a), and similarly yields hydroxylated products with manifold 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 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 manifold labdane-related diterpenes.

SUBMITTER: Jia M

PROVIDER: S-EPMC5921835 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Jia Meirong M O'Brien Terrence E TE Zhang Yue Y Siegel Justin B JB Tantillo Dean J DJ Peters Reuben J RJ

ACS catalysis 20180308 4

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 manifold 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 selective production of (13S)-sclareol (2 ...[more]

PMID: 29713562

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