MICROBIAL-PRODUCTION OF ANTIBIOTIC FOSFOMYCIN BY A STEREOSELECTIVE EPOXIDATION AND ITS FORMATION MECHANISM

Fifteen strains of aerobic bacteria and two actinomycetous strains wer e isolated from various soil samples, using cis-propenylphosphonic aci d as the sole source of carbon. Taxonomic studies showed that these be longed to the Pseudomonas, Alcaligenes, Flavobacterium, Aeromonas, Cor ynebacterium and Streptomyces genera. Most of these strains produced t he antibiotic fosfomycin [(-)-(1R, 2S)-1,2-epoxypropylphosphonic acid] from cis-propenylphosphonic acid by stereoselective epoxidation. Unde r the culture conditions tested, the production of fosfomycin reached a level of 2.0 mg/ml and 0.75 mg/ml by F. esteroaromaticum IFO 3751 an d P. putida IK-8 respectively. Purified fosfomycin was an active stere oisomer and its optical purity was a little higher than that of the sy nthetic compound. Although the stereoespecificity of each enzyme parti cipating in the epoxidation reaction has not yet been clarified, the e poxide formation proceeded through a bromohydrin intermediate produced by bromoperoxidase, finally yielding fosfomycin by the action of halo hydrin epoxidase.