Isofunctional but Structurally Different Methyltransferases for Dithiolopyrrolone Diversification

Abstract: Dithiolopyrrolone (DTP) natural products are produced by several different bacteria and have potent antibacterial, antifungal and anticancer activities. While the amide of their DTP core can be methylated to fine‐tune bioactivity, the enzyme responsible for the amide N‐methylation has remained elusive in most taxa. Here, we identified the amide methyltransferase XrdM that is responsible for xenorhabdin (XRD) methylation in Xenorhabdus doucetiae but encoded outside of the XRD gene cluster. XrdM turned out to be isofunctional with the recently reported methyltransferase DtpM, that is involved in the biosynthesis of the DTP thiolutin, although its X‐ray structure is unrelated to that of DtpM. To investigate the structural basis for ligand binding in both enzymes, we used X‐ray crystallography, modeling, site‐directed mutagenesis, and kinetic activity assays. Our study expands the limited knowledge of post‐non‐ribosomal peptide synthetase (NRPS) amide methylation in DTP biosynthesis and reveals an example of convergent evolution of two structurally completely different enzymes for the same reaction in different organisms.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Isofunctional but Structurally Different Methyltransferases for Dithiolopyrrolone Diversification ; day:18 ; month:10 ; year:2024 ; extent:10 ; Angewandte Chemie ; (18.10.2024) (gesamt 10)

Contributors, Places and Time

• Creator: Su, Li ; Huber, Eva M. ; Westphalen, Margaretha ; Gellner, Jonas ; Bode, Edna ; Köbel, Tania ; Grün, Peter ; Alanjary, Mohammad ; Glatter, Timo ; Cirnski, Katarina ; Müller, Rolf ; Schindler, Daniel ; Groll, Michael ; Bode, Helge Björn

Further information

• DOI: 10.1002/ange.202410799
• URN: urn:nbn:de:101:1-2410181516551.403933816402
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:23 AM CEST