Catalysis

Discovery and Characterization of a Terpene Biosynthetic Pathway featuring a Norbornene-forming Diels-Alderase

Authors

  • Zuodong Sun University of California, Los Angeles ,
  • Cooper Jamieson University of California, Los Angeles ,
  • Masao Ohashi University of California, Los Angeles - United States ,
  • Kendall Houk University of California, Los Angeles - United States ,
  • Yi Tang University of California, Los Angeles - United States

Abstract

Pericyclases, enzymes that catalyze pericyclic reactions, form an expanding family of enzymes that have biocatalytic utility. Despite the increasing number of pericyclases discovered, the Diels-Alder (DA) cyclization between a cyclopentadiene and an olefinic dienophile to form norbornene, which is among the best-studied cycloadditions in synthetic chemistry, has surprisingly no enzymatic counterpart to date. Here we report the discovery of a pathway featuring a norbornene synthase SdnG for the biosynthesis of sordaricin-the terpene precursor of antifungal natural product sordarin. Full reconstitution of sordaricin biosynthesis revealed a concise oxidative strategy used by Nature to transform an entirely hydrocarbon precursor into the highly functionalized substrate of SdnG for intramolecular Diels-Alder (IMDA) cycloaddition. SdnG generates the norbornene core of sordaricin and accelerates this reaction to suppress host-mediated redox modifications of the activated dienophile. Findings from this work expand the scopes of pericyclase-catalyzed reactions and P450-mediated terpene maturation.

Content

Thumbnail image of Sordaricin main text Final rv1 without track change.pdf

Supplementary material

Thumbnail image of Sordaricin SI Final rv1 without trach change.pdf
Supplementary Information for Discovery and Characterization of a Terpene Biosynthetic Pathway featuring a Norbornene-forming Diels-Alderase
Supplementary Information including supplementary Notes, Tables, Figures, and the molecular coordinates of all calculated structures.