Mechanism of Action of O-Carbamyl-D-Serine

Abstract

O-Carbamyl-D-serine, NH₂-CO-O-CH₂-CH(NH₂)-COOH, was first isolated from a Streptomyces by Hagemann et al.¹⁾ Skinner et al.²⁾ synthesized the L-isomer, which was reported to inhibit purine biosynthesis as a L-glutamine antagonist. An antibiotic, which showed stronger inhibition on a synthetic medium against B. subtilis than on a nutrient agar, was isolated from a strain closely related to Streptomyces fragilis by Okami et al,³⁾ and was confirmed to be O-carbamyl-D-serine. They obtained this substance in a screening studies for antibiotics having an inhibitory activity against a mutant of B. subtilis requiring adenine, cytosine and uracil.

O-Carbamyl-D-serine was obtained in our laboratory from culture filtrates of a certain strains of Streptomycetes in the course of screening for D-alanine antagonists. Further studies revealed that this antibiotic selectively inhibits the biosynthesis of bacterial cell walls as described with penicillin, D-4-amino-3-isoxazolidone, vancomycin, bacitracin and novobiocin. A review of studies with these antibiotics was recently published by Perkins⁵⁾. The molecular model of O-carbamyl-D-serine indicated a stereochemical structure, related to D-alanine or D-4-amino-3-isoxazolidone. Investigations of the synergistic activity with other antibiotics and mouse protection tests against Staph. Aureus by O-carbamyl-D-serine were also carried out. The results are presented in this publication.