Inhibition of bacterial isoprenoid synthesis by fosmidomycin, a phosphonic acid-containing antibiotic

The mechanism of action of fosmidomycin (FR-31564), a phosphonic acid containing antibiotic, was examined against Escherichia coli, Micrococcus luteus and other bacteria. It converted growing Esch. coli cells into spheroplasts or swollen cells, but did not inhibit the enzymatic reactions of cell wall synthesis in ether-treated cells. Unlike bicyclomycin, phenethyl alcohol and mitomycin C, it did not reduce the amount of envelope lipoprotein, phospholipids, or DNA, but did reduce the amount of menaquinones and ubiquinones in growing Esch. coli cells. It also inhibited the biosynthesis of both carotenoids and menaquinones in M. luteus cells, suggesting that inhibition of the biosynthesis of a common precursor of these isoprenoids (possibly farnesyl pyrophosphate) might be the main site of its antibacterial activity.