A Carbamoyl -Methyltransferase Catalyzes -Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis.
Fuente:
PubMed
Enregistré dans:
| Auteurs principaux: | , , , , , , |
|---|---|
| Format: | Artículo científico |
| Langue: | en |
| Publié: |
Journal of the American Chemical Society
2025
|
| Sujets: | |
| Accès en ligne: | |
| Tags: |
Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
|
| _version_ | 1868266184076427264 |
|---|---|
| author | Li, Zhongyue Yang, Wanting Sun, Zhonglin Wang, Haoxin Lu, Chunhua Zhu, Deyu Shen, Yuemao |
| author_facet | Li, Zhongyue Yang, Wanting Sun, Zhonglin Wang, Haoxin Lu, Chunhua Zhu, Deyu Shen, Yuemao Li, Zhongyue Yang, Wanting Sun, Zhonglin Wang, Haoxin Lu, Chunhua Zhu, Deyu Shen, Yuemao |
| collection | PubMed - marine biology |
| contents | A Carbamoyl -Methyltransferase Catalyzes -Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis. Li, Zhongyue Yang, Wanting Sun, Zhonglin Wang, Haoxin Lu, Chunhua Zhu, Deyu Shen, Yuemao Amides Methyltransferases Methylation Humans Maytansine Biocatalysis Molecular Structure Antineoplastic Agents Cell Line, Tumor Primary amide-specific -methyltransferases are extremely scarce in microbial secondary metabolism. Here, Asc-Orf2, an -methyltransferase involved in the biosynthesis of ansacarbamitocins, was identified to catalyze the methylation of the 3--carbamoyl moiety. Structural analysis identified an unprecedented NPPH catalytic motif, offering a mechanistic basis to overcome the chemical inertness of primary amides. The 3--(-methyl)-carbamoyl maytansinoid derivatives, modified 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 -allylated carbamoyl maytansinoid derivative optimized for antibody-drug conjugate payload. |
| format | Artículo científico |
| id | pubmed_40601550 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Journal of the American Chemical Society |
| record_format | pubmed |
| spellingShingle | A Carbamoyl -Methyltransferase Catalyzes -Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis. Li, Zhongyue Yang, Wanting Sun, Zhonglin Wang, Haoxin Lu, Chunhua Zhu, Deyu Shen, Yuemao Amides Methyltransferases Methylation Humans Maytansine Biocatalysis Molecular Structure Antineoplastic Agents Cell Line, Tumor A Carbamoyl -Methyltransferase Catalyzes -Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis. Li, Zhongyue Yang, Wanting Sun, Zhonglin Wang, Haoxin Lu, Chunhua Zhu, Deyu Shen, Yuemao Amides Methyltransferases Methylation Humans Maytansine Biocatalysis Molecular Structure Antineoplastic Agents Cell Line, Tumor Primary amide-specific -methyltransferases are extremely scarce in microbial secondary metabolism. Here, Asc-Orf2, an -methyltransferase involved in the biosynthesis of ansacarbamitocins, was identified to catalyze the methylation of the 3--carbamoyl moiety. Structural analysis identified an unprecedented NPPH catalytic motif, offering a mechanistic basis to overcome the chemical inertness of primary amides. The 3--(-methyl)-carbamoyl maytansinoid derivatives, modified 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 -allylated carbamoyl maytansinoid derivative optimized for antibody-drug conjugate payload. |
| title | A Carbamoyl -Methyltransferase Catalyzes -Methylation of the Primary Amide in Ansacarbamitocin Biosynthesis. |
| topic | Amides Methyltransferases Methylation Humans Maytansine Biocatalysis Molecular Structure Antineoplastic Agents Cell Line, Tumor |
| url | https://pubmed.ncbi.nlm.nih.gov/40601550/ |