Dokument: Re‐engineering a transferase scaffold for indole C3 methylation in diketopiperazines
| Titel: | Re‐engineering a transferase scaffold for indole C3 methylation in diketopiperazines | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=70755 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250915-111807-6 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Haase, Mona [Autor] Weiergräber, Oliver H. [Autor] Pietruszka, Jörg [Autor] | |||||||
| Dateien: |
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| Stichwörter: | methyltransferase , crystal structure , pyrroloindole natural product , rational design , biocatalysis | |||||||
| Beschreibung: | The pyrroloindole (hexahydropyrrolo[2,3-b]indole, HPI) structural motif is present in a wide range of natural products with various biological activities, yet its chemical synthesis poses a challenge, particularly regarding methylation at the indole C3 position. In nature, S-adenosyl methionine (SAM)-dependent methyltransferases efficiently catalyze this reaction with high
stereoselectivity. This study presents the investigation and rational redesign of a potential methyltransferase, termed SeMT, from the actinomycete Saccharopolyspora erythraea. While its threedimensional structure elucidated via X-ray crystallography confirmed extensive structural similarity to cyclic dipeptideprocessing methyltransferases such as SgMT, its putative catalytic center is clearly divergent. Accordingly, wild-type SeMT displayed minimal activity with diketopiperazine (DKP) substrates, triggering an extensive mutagenesis effort aimed at iteratively enhancing this methyltransferase function. This work yielded a variant with appreciable activity, which was comprehensively characterized. Notably, a specific mutation within the catalytic triad of SeMT proved critical not only for its own function but also for the temperature-activity profile of its homolog protein SgMT. Beyond the specific properties of SeMT, these findings hence provide important insights into the active center architecture of indole C3-methyltransferases, supporting further development of these enzymes into refined biocatalysts for synthetic applications. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Haase, M., Weiergräber, O. H., & Pietruszka, J. (2025). Re‐engineering a transferase scaffold for indole | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 15.09.2025 | |||||||
| Dateien geändert am: | 15.09.2025 |
