Studies on the biodegradation of fosfomycin: Growth of Rhizobium huakuii PMY1 on possible intermediates synthesised chemically

Abstract

The first step of the mineralisation of fosfomycin by R. huakuii PMY1 is hydrolytic ring opening with the formation of (1R,2R)-1,2-dihydroxypropylphosphonic acid. This phosphonic acid and its three stereoisomers were synthesised by chemical means and tested as their ammonium salts for mineralisation as evidenced by release of P_i. Only the (1R,2R)-isomer was degraded. A number of salts of phosphonic acids such as (±)-1,2-epoxybutyl-, (±)-1,2-dihydroxyethyl-, 2-oxopropyl-, (S)-2-hydroxypropyl-, (±)-1-hydroxypropyl- and (±)-1-hydroxy-2-oxopropylphosphonic acid were synthesised chemically, but none supported growth. In vitro C–P bond cleavage activity was however detected with the last phosphonic acid. A mechanism involving phosphite had to be discarded as it could not be used as a phosphorus source. R. huakuii PMY1 grew well on (R)- and (S)-lactic acid and hydroxyacetone, but less well on propionic acid and not on acetone or (R)- and (±)-1,2-propanediol. The P_i released from (1R,2R)-1,2-dihydroxypropylphosphonic acid labelled with one oxygen-18 in the PO₃H₂group did not stay long enough in the cells to allow complete exchange of ¹⁸O for ¹⁶O by enzymic turnover.