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January 24, 20260 citations

Exploring a Unique Class II Diterpene Cyclase: The Modified Catalytic Acid Motif Contributes to Ring Contraction in Premutilin Synthase.

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KHKristin HelwigJXJun XieCLCody Lemke

Key Points

  • To investigate how a unique variant of the catalytic acid motif in a diterpene cyclase influences product formation.
  • Substitution of aspartate for methionine in the enzyme
  • Analysis of product formation using biochemical assays
  • Characterization of resulting compounds through chemical analysis
  • Production of mutildienyl pyrophosphate (MPP) is largely blocked by the substitution
  • A novel hydroxylated product, syn-halima-13E-en-5β-ol-15-PP, is produced instead
  • This highlights the importance of the specific catalytic acid motif in product specificity.

Abstract

The class II diterpene cyclase from pleuromutilin biosynthesis contains a unique variant of the otherwise highly conserved DxDD motif (DxDM), which cooperatively serves as the catalytic acid, and uniquely produces an "A" ring contracted product, mutildienyl pyrophosphate (MPP). The correlation between these features was investigated here via substitution of aspartate for methionine, which largely blocks the production of MPP and leads to a novel hydroxylated product, syn-halima-13E-en-5β-ol-15-PP, providing insight into this unique reaction.

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Cite This Study

Helwig et al. (2026) studied this question.

synapsesocial.com/papers/69746187bb9d90c67120b593https://doi.org/10.1021/acs.orglett.5c04898
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Magnesium-specific ring expansion/contraction catalysed by the class II diterpene cyclase from pleuromutilin biosynthesis2020 · 6 citations
  2. 2Premutilin Synthase: Ring Rearrangement by a Class II Diterpene Cyclase2018 · 33 citations
  3. 3Functiona l Analysis of Eubacterial Diterpene Cyclases Responsible for Biosynthesis of a Diterpene Antibiotic, Terpentecin2002 · 92 citations
  4. 4Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi2017 · 79 citations
  5. 5Functional Analysis of the DXDDTA Motif in Squalene-Hopene Cyclase by Site-directed Mutagenesis Experiments: Initiation Site of the Polycyclization Reaction and Stabilization Site of the Carbocation Intermediate of the Initially Cyclized A-Ring1999 · 72 citations