8rdn

Publication Abstract from PubMed

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.

Isofunctional but Structurally Different Methyltransferases for Dithiolopyrrolone Diversification.,Su L, Huber EM, Westphalen M, Gellner J, Bode E, Kobel T, Grun P, Alanjary MM, Glatter T, Cirnski K, Muller R, Schindler D, Groll M, Bode HB Angew Chem Int Ed Engl. 2024 Aug 26:e202410799. doi: 10.1002/anie.202410799. PMID:39185606^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.