ArticleACS chemical biology2017
A Pair of Residues That Interactively Affect Diterpene Synthase Product Outcome.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Engineered microorganisms unlock a new era of diterpenoid biomanufacturing: recent advances and future perspectives.Bioresources and bioprocessing · 2026Review
- Structural diversity of isoprene synthases in mosses from multiple terpenoid synthase lineages.The Journal of biological chemistry · 2026Article
- Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues.Chemical communications (Cambridge, England) · 2025Review
- From functional plasticity of two diterpene synthases (IrTPS2/IrKSL3a) to enzyme evolution.ACS catalysis · 2024Article
- Sequence-Structure Analysis Unlocking the Potential Functional Application of the Local 3D Motifs of Plant-Derived Diterpene Synthases.Biomolecules · 2024Article
- Decoding Catalysis by Terpene Synthases.ACS catalysis · 2023Review
- Mechanistic analysis for the origin of diverse diterpenes inActa pharmaceutica Sinica. B · 2022Article
- Diterpene synthases from Leonurus japonicus elucidate epoxy-bridge formation of spiro-labdane diterpenoids.Plant physiology · 2022Article
- A pair of threonines mark ent-kaurene synthases for phytohormone biosynthesis.Phytochemistry · 2021Article
- Engineering of Ancestors as a Tool to Elucidate Structure, Mechanism, and Specificity of Extant Terpene Cyclase.Journal of the American Chemical Society · 2021Article
- Combinatorial biosynthesis and the basis for substrate promiscuity in class I diterpene synthases.Metabolic engineering · 2019Article
- A database-driven approach identifies additional diterpene synthase activities in the mint family (Lamiaceae).The Journal of biological chemistry · 2019Article
- Terpene Synthases as Metabolic Gatekeepers in the Evolution of Plant Terpenoid Chemical Diversity.Frontiers in plant science · 2019Review
- Changing Face: A Key Residue for the Addition of Water by Sclareol Synthase.ACS catalysis · 2018Article
- Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches.Frontiers in chemistry · 2018Article
- Functional Characterization of Two Class II Diterpene Synthases Indicates Additional Specialized Diterpenoid Pathways in Maize (Frontiers in plant science · 2018Article
- Exploring the Influence of Domain Architecture on the Catalytic Function of Diterpene Synthases.Biochemistry · 2017Article
- Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases.PloS one · 2017Article
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Authors and funding
5 authors at 1 institution in 2 countries.
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Abstract
The labdane-related diterpenoids (LRDs) are an important superfamily of natural products whose structural diversity critically depends on the hydrocarbon skeletal structures generated, in large part, by class I diterpene synthases. In the plant kingdom, where the LRDs are predominantly found, the relevant class I diterpene synthases are clearly derived from the ent-kaurene synthase (KS) required in all land plants for phytohormone biosynthesis and, hence, are often termed KS-like (KSL). Previous work, initiated by the distinct function of two alleles of a KSL from rice, OsKSL5, identified a single residue switch with a profound effect on not only OsKSL5 product outcome but also that of land plant KSs more broadly, specifically, replacement of a key isoleucine with threonine, which interrupts formation of the tetracyclic ent-isokaurene at the tricyclic stage, leading to production of ent-pimaradiene instead. Here, further studies of these alleles led to discovery of another, nearby residue that tunes product outcome. Substitution for this newly identified residue is additionally shown to exert an epistatic effect in KSs, altering product distribution only if combined with replacement of the key isoleucine. On the other hand, this pair of residues was found to exert additive effects on the product outcome mediated by distantly related KSLs from the eudicot castor bean. Accordingly, it was possible to use a rational combination of substitutions for this pair of residues to engineer significantly increased (dominant) selectivity for novel 8α-hydroxy-ent-pimar-15-ene product outcome in the KS from the dicot Arabidopsis thaliana, demonstrating the utility of these results.
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