Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis

Hyun Bong Park, Parthasarathy Sampathkumar, Corey E. Perez, Joon Ha Lee, Jeannie Tran, Jeffrey B. Bonanno, Elissa A. Hallem, Steven C. Almo, Jason M. Crawford

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Members of the gammaproteobacterial Photorhabdus genus share mutualistic relationships with Heterorhabditis nematodes, and the pairs infect a wide swath of insect larvae. Photorhabdus species produce a family of stilbenes, with two major components being 3,5-dihydroxy-4-isopropyl-trans-stilbene (compound 1) and its stilbene epoxide (compound 2). This family of molecules harbors antimicrobial and immunosuppressive activities, and its pathway is responsible for producing a nematode "food signal" involved in nematode development. However, stilbene epoxidation biosynthesis and its biological roles remain unknown. Here, we identified an orphan protein (Plu2236) from Photorhabdus luminescens that catalyzes stilbeneepoxidation.Structural,mutational,andbiochemicalanalyses confirmed the enzyme adopts a fold common to FADdependent monooxygenases, contains a tightly bound FAD prosthetic group, and is required for the stereoselective epoxidation of compounds 1 and 2. The epoxidase gene was dispensable in a nematode-infective juvenile recovery assay, indicating the oxidized compound is not required for the food signal. The epoxide exhibited reduced cytotoxicity toward its producer, suggesting this may be a natural route for intracellular detoxification. In an insect infection model, we also observed two stilbene-derived metabolites that were dependent on the epoxidase. NMR, computational, and chemical degradation studies established their structures as new stilbene-L-proline conjugates, prolbenes A (compound 3) and B (compound 4). The prolbenes lacked immunosuppressive and antimicrobial activities comparedwiththeirstilbenesubstrates,suggestingametabolite attenuation mechanism in the animal model. Collectively, our studies provide a structural view for stereoselective stilbene epoxidation and functionalization in an invertebrate animal infection model and provide new insights into stilbene cellular detoxification.

Original languageEnglish (US)
Pages (from-to)6680-6694
Number of pages15
JournalJournal of Biological Chemistry
Issue number16
StatePublished - Apr 21 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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