An Iterative O‐Methyltransferase Catalyzes 1,11‐Dimethylation of Aspergillus fumigatus Fumaric Acid Amides |
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| Authors: | Dr. Daniel Kalb Dr. Thorsten Heinekamp Dr. Sebastian Schieferdecker Prof. Dr. Markus Nett Prof. Dr. Axel A. Brakhage Prof. Dr. Dirk Hoffmeister |
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| Affiliation: | 1. Department Pharmaceutical Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Friedrich Schiller University, Jena, Germany;2. Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Friedrich Schiller University, Jena, Germany;3. Research Group Secondary Metabolism of Predatory Bacteria, Leibniz Institute for Natural Product Research and Infection Biology, Friedrich Schiller University, Jena, Germany;4. Department of Biochemical and Chemical Engineering, Technical University Dortmund, Dortmund, Germany |
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| Abstract: | S‐adenosyl‐l ‐methionine (SAM)‐dependent methyltransfer is a common biosynthetic strategy to modify natural products. We investigated the previously uncharacterized Aspergillus fumigatus methyltransferase FtpM, which is encoded next to the bimodular fumaric acid amide synthetase FtpA. Structure elucidation of two new A. fumigatus natural products, the 1,11‐dimethyl esters of fumaryl‐l ‐tyrosine and fumaryl‐l ‐phenylalanine, together with ftpM gene disruption suggested that FtpM catalyzes iterative methylation. Final evidence that a single enzyme repeatedly acts on fumaric acid amides came from an in vitro biochemical investigation with recombinantly produced FtpM. Size‐exclusion chromatography indicated that this methyltransferase is active as a dimer. As ftpA and ftpM homologues are found clustered in other fungi, we expect our work will help to identify and annotate natural product biosynthesis genes in various species. |
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| Keywords: | Aspergillus fumigatus biosynthesis fumaric acid methyltransferase natural products |
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