Studies on the biodegradation of fosfomycin: growth of Rhizobium huakuii PMY1 on possible intermediates synthesised chemically.
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 PO3H2 group did not stay long enough in the cells to allow complete exchange of 18O for 16O by enzymic turnover.
McGrath
John W
JW
School of Biology and Biochemistry, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Rd., Belfast, BT9 7BL, Northern Ireland.
Hammerschmidt
Friedrich
F
Preusser
Werner
W
Quinn
John P
JP
Schweifer
Anna
A
D004851:Epoxide Hydrolases / Q000378:metabolism; D005027:Ethylene Oxide / Q000737:chemistry; D005578:Fosfomycin / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D012231:Rhizobium / Q000254:growth & development* / Q000378:metabolism*; D013237:Stereoisomerism
D005578:Fosfomycin; D004851:Epoxide Hydrolases; D005027:Ethylene Oxide