Enzymatic Synthesis of Kynurenic Acid-Linked Dipeptides with C-Terminal Amide
Abstract
Kynurenic acid (KYNA) ester/amide derivatives were explored for improved biological potency. Herein, we report the discovery of a nonribosomal peptide synthase and P450 enzyme cascade capable of synthesizing KYNA-linked dipeptides in Aspergillus nidulans . In vitro assay together with isotope feeding experiments reveals an intriguing rearrangement from diketopiperazine (DKP) to dipeptide with a C-terminal amide. Feeding tryptophan derivatives allows the generation of various KYNA ester/amide derivatives. Our findings reveal the natural enzymatic machinery for KYNA amide biosynthesis, establishing a foundation for enzymatic access to KYNA amide derivatives.
Fields of Study & Subjects
Microbial Natural Products and Biosynthesis
Tryptophan and brain disorders
Enzyme Catalysis and Immobilization
Publication details
- Journal / source
- ACS Catalysis
- Volume
- 16
- Issue
- 5
- Pages
- 4355–4361
- Publication date
- 17 February 2026
- Language
- EN