Biosynthesis of natural products with a P–C bond. Part 8: on the origin of the oxirane oxygen atom of fosfomycin in Streptomyces fradiae

Abstract

(R, S)-, (R)- and (S)-(2-Hydroxy-[1, 1-²H₂]propyl)phosphonic acid were fed to Streptomyces fradiae producing fosfomycin isolated as the corresponding ring-opened aminophosphonic acid. Only (S)(2-hydroxy-[1,1-²H₂]propyl)phosphonic acid was efficiently incorporated into fosfomycin (37% deuterium at C-1 of the aminophosphonic acid). (R,S)-(2-[¹⁸O]Hydroxypropyl)phosphonic acid gave [1-¹⁸O]aminophosphonic acid. None of the four stereoisomeric (1,2-dihydroxy-[1-²H₁]propyl)phosphonic acids labelled fosfomycin. Both (1R,2S)- and (1S,2S)-(1,2-dihydroxy-[1-³H]propyl)phosphonic acid were taken up into the cells, but were not specifically incorporated into fosfomycin, the dilution of radioactivity being 0.02 and 0.01%, respectively. Obviously they are not intermediates of the biosynthesis of fosfomycin.