Structural highlights
Function
A0A229RJG8_AMYAL
Publication Abstract from PubMed
Primary amide-specific N-methyltransferases are extremely scarce in microbial secondary metabolism. Here, Asc-Orf2, an N-methyltransferase involved in the biosynthesis of ansacarbamitocins, was identified to catalyze the methylation of the 3-O-carbamoyl moiety. Structural analysis identified an unprecedented NPPH catalytic motif, offering a mechanistic basis to overcome the chemical inertness of primary amides. The 3-O-(N-methyl)-carbamoyl maytansinoid derivatives, modified via Asc-Orf2-catalyzed methylation, exhibited markedly enhanced antitumor activity, highlighting the magic methylation effect in bioactivity modulation. Furthermore, structure-targeted engineering expanded the catalytic scope of Asc-Orf2, enabling the directed synthesis of an N-allylated carbamoyl maytansinoid derivative optimized for antibody-drug conjugate payload.
A Carbamoyl N-Methyltransferase Catalyzes N-Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis.,Li Z, Yang W, Sun Z, Wang H, Lu C, Zhu D, Shen Y J Am Chem Soc. 2025 Jul 16;147(28):24186-24192. doi: 10.1021/jacs.5c05398. Epub , 2025 Jul 2. PMID:40601550[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li Z, Yang W, Sun Z, Wang H, Lu C, Zhu D, Shen Y. A Carbamoyl N-Methyltransferase Catalyzes N-Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis. J Am Chem Soc. 2025 Jul 16;147(28):24186-24192. PMID:40601550 doi:10.1021/jacs.5c05398
