PMP-diketopiperazine adducts form at the active site of a PLP dependent enzyme involved in formycin biosynthesis

• Published in: Chemical communications (Cambridge, England) Vol. 55; no. 96; pp. 1452 - 1455
• Main Authors: Gao, Sisi, Liu, Huanting, de Crécy-Lagard, Valérie, Zhu, Wen, Richards, Nigel G. J, Naismith, James H
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 28.11.2019
• Subjects: Adducts; Antibiotics; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biocatalysis; Biosynthesis; Catalytic Domain; Cycloserine - chemistry; Diketopiperazines - chemistry; Diketopiperazines - metabolism; Enzymes; Formycins - biosynthesis; Formycins - chemistry; Hydrogen-Ion Concentration; Organic chemistry; Pyridoxal Phosphate - chemistry; Pyridoxamine - analogs & derivatives; Pyridoxamine - chemistry; Pyridoxamine - metabolism; Streptomyces - chemistry; Streptomyces - metabolism; Transaminases - antagonists & inhibitors; Transaminases - genetics; Transaminases - metabolism
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c9cc06975e

ForI is a PLP-dependent enzyme from the biosynthetic pathway of the C-nucleoside antibiotic formycin. Cycloserine is thought to inhibit PLP-dependent enzymes by irreversibly forming a PMP-isoxazole. We now report that ForI forms novel PMP-diketopiperazine derivatives following incubation with both d and l cycloserine. This unexpected result suggests chemical diversity in the chemistry of cycloserine inhibition. ForI is a PLP-dependent enzyme from the biosynthetic pathway of the C-nucleoside antibiotic formycin.