Sodorifen Biosynthesis in the Rhizobacterium Serratia plymuthica Involves Methylation and Cyclization of MEP-Derived Farnesyl Pyrophosphate by a SAM-Dependent C-Methyltransferase

Stephan Von Reuss, Dajana Domik, Marie Chantal Lemfack, Nancy Magnus, Marco Kai, Teresa Weise, Birgit Piechulla

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The rhizobacterium Serratia plymuthica 4Rx13 releases a unique polymethylated hydrocarbon (C16H26) 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 C16 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 13C-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. 13C{1H} NMR spectroscopy facilitated the localization of 13C labels and provided detailed insights into the biosynthetic pathway from FPP via pre-sodorifen pyrophosphate to sodorifen.

Original languageEnglish (US)
Pages (from-to)11855-11862
Number of pages8
JournalJournal of the American Chemical Society
Volume140
Issue number37
DOIs
StatePublished - Sep 19 2018

Bibliographical note

Funding Information:
Support by the Deutsche Forschungsgemeinschaft (DFG) (Pi153/28-1 and 36-1), the University of Rostock, the Max Planck Society (MPG), the University of Neuchatel (UniNE), and the Swiss National Science Foundation (SNSF) is gratefully acknowledged. We thank Claudia Dinse and Do.rte Warber for technical assistance

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