This pathway was contributed by David Joseph De Grio and John Schrom, BioC/MicE 5309 at the University of Minnesota.
Fosfomycin is an antibiotic used in a single dose to treat urinary tract, respiratory, intraabdominal, obstetric-gynecologic, CNS and osetoarticular infections (PubChem and Gobernato et al., 2003). It is successful in 80% of cases and shows very few side effects (Gobernato et al., 2003). Adverse side effects, mainly liver toxicity, have been observed in patients with cystic fibrosis (Durupt et al., 2001). Bacterial resistance has been observed (Fillgrove et al., 2003 and Marchese et al., 2003). Because of microbial resistance, some other drugs can no longer be recommended as reliable agents. Fosfomycin remains a drug of choice for the eradication of many uncomplicated infections.
This antibiotic is biosynthesized by Streptomyces from (S)-2-hydroxypropylphosphonic acid (Liu et al., 2004). The biodegradation was initially studied in Listeria monocytogenese, but similar degradation pathways occur in many bacterial pathogens. When biodegraded, Mn(II)-dependent thiol transferases add cysteine or glutathiol residues across the epoxy bond (Fillgrove et al., 2003).
The following is a text-format fosfomycin degradation pathway map. Organisms which can initiate the pathway are given, but other organisms may also carry out later steps. Follow the links for more information on compounds or reactions. This map is also available in graphic (9k) format.
Fosfomycin Fosfomycin Fosfomycin
Pseudomonas aeruginosa Rhizobium huakuii Listeria monocytogenes
| PMY1 |
| | |
| glutathione | cysteine |
| transferase | transferase | epoxide hydrolase
| | |
| | |
v v v
Hydrogen (1R,2R)- Hydrogen (1R,2R)- Hydrogen (1R,2R)-
1-glutathiol-2-hydroxy 1-L-Cysteine,2-hydroxy 1,2-dihydroxy
propylphosphonic acid propylphosphonic acid propylphosphonic acid
Page Author(s): David Joseph De Grio, John Schrom, and Dave Roe
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