| Title: | Sodorifen Biosynthesis in the Rhizobacterium Serratia plymuthica Involves Methylation and Cyclization of MEP-Derived Farnesyl Pyrophosphate by a SAM-Dependent C-Methyltransferase |
| Author(s): | von Reuss S; Domik D; Lemfack MC; Magnus N; Kai M; Weise T; Piechulla B; |
| Address: | "Laboratory for Bioanalytical Chemistry, Institute of Chemistry , University of Neuchatel , Avenue de Bellevaux 51 , CH-2000 Neuchatel , Switzerland. Department of Bioorganic Chemistry , Max Planck Institute for Chemical Ecology , Hans-Knoell-Strasse 8 , D-07745 Jena , Germany. Institute for Biological Sciences , University of Rostock , Albert-Einstein-Strasse 3 , D-18059 Rostock , Germany" |
| ISSN/ISBN: | 1520-5126 (Electronic) 0002-7863 (Linking) |
| Abstract: | "The rhizobacterium Serratia plymuthica 4Rx13 releases a unique polymethylated hydrocarbon (C(16)H(26)) with a bicyclo[3.2.1]octadiene skeleton called sodorifen. Sodorifen production depends on a gene cluster carrying a C-methyltransferase and a terpene cyclase along with two enzymes of the 2- C-methyl-d-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis. Comparative analysis of wild-type and mutant volatile organic compound profiles revealed a C-methyltransferase-dependent C(16) alcohol called pre-sodorifen, the production of which is upregulated in the terpene cyclase mutant. The monocyclic structure of this putative intermediate in sodorifen biosynthesis was identified by NMR spectroscopy. In vitro assays with the heterologously expressed S. plymuthica C-methyltransferase and terpene cyclase demonstrated that these enzymes act sequentially to convert farnesyl pyrophosphate (FPP) into sodorifen via a pre-sodorifen pyrophosphate intermediate, indicating that the S-adenosyl methionine (SAM)-dependent C-methyltransferase from S. plymuthica exhibits unprecedented cyclase activity. In vivo incorporation experiments with (13)C-labeled succinate, l-alanine, and l-methionine confirmed a MEP pathway to FPP via the canonical glyceraldehyde-3-phosphate and pyruvate, as well as its SAM-dependent methylation in pre-sodorifen and sodorifen biosynthesis. (13)C(1)H NMR spectroscopy facilitated the localization of (13)C labels and provided detailed insights into the biosynthetic pathway from FPP via pre-sodorifen pyrophosphate to sodorifen" |
| Keywords: | Bridged Bicyclo Compounds/chemistry/*metabolism Cyclization Erythritol/*analogs & derivatives/chemistry/metabolism Methylation Methyltransferases/*metabolism Molecular Structure Octanes/chemistry/*metabolism Polyisoprenyl Phosphates/chemistry/*metabolism; |
| Notes: | "Medlinevon Reuss, Stephan Domik, Dajana Lemfack, Marie Chantal Magnus, Nancy Kai, Marco Weise, Teresa Piechulla, Birgit eng Research Support, Non-U.S. Gov't 2018/08/23 J Am Chem Soc. 2018 Sep 19; 140(37):11855-11862. doi: 10.1021/jacs.8b08510. Epub 2018 Sep 4" |
