Work

Discovery and characterization of a terpene biosynthetic pathway featuring a norbornene-forming Diels-Alderase

Year: 2022

Type: article

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 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 reveals a concise oxidative strategy used by Nature to transform an entirely hydrocarbon precursor into the highly functionalized substrate of SdnG for intramolecular Diels-Alder 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.

Source: Nature Communications

DOI: 10.1038/s41467-022-30288-6

Authors: Zuodong Sun, Cooper S. Jamieson, Masao Ohashi, K. N. Houk, Yi Tang

Institution: University of California, Los Angeles

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $5,890

Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases