FR900098, an analog of the naturally occurring antibiotic Fosmidomycin, inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an enzyme in the non-mevanolate pathway for isoprenoid biosynthesis. The non-mevanolate, or MEP, pathway is essential in gram-negative, some gram-positive bacteria, plants, and protozoa making it an attractive pathway to target for antibiotics since mammals use the mevalonate pathway to synthesize isoprenoids. FR900098 is twice as effective as Fosmidomycin against P. faliciparum in vitro.

References

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1) E. Iguchi, et al. “Studies on new phosphonic acid antibiotics. II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds” The Journal of Antibiotics 33, 1980, 19–23.2)H. Jomaa, et al. “Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.” Science, 285, 1999, 1573-1576.3) T. Umeda, et al. “Molecular Basis of Fosmidomycin’s action on the Human Parasite Plasmodium falciparum” Sci. Rep., 1, 2011, doi:10.1038/srep00009.

Keywords: [3-(N-hydroxyacetamido)-propyl)phosphonate) sodium salt], Malaria, non-mevalonate, MEP, DXR