InterPro domain: IPR024192

This entry represents a group of isopentenyl phosphate kinases (IPKs). They catalyze the formation of isopentenyl diphosphate (IPP), the building block of all isoprenoids [ 1 ]. This entry also includes FomA protein from Streptomyces.

Fosfomycin (L-(cis)-1,2-epoxy propyl phosphonic acid) is an antibiotic produced by some species of Streptomyces and Pseudomonas. As an analogue of phosphoenolpyruvate (PEP), this compound irreversibly inhibits PEP UDP-N-acetylglucosamine-3-O-enolpyruvyltransferase (enolpyruvyltransferase), which catalyses the first step of peptidoglycan biosynthesis [ 2 ]. FomA is one of the fosfomycin resistance kinases. Together with FomB (encoded in the fosfomycin biosynthetic gene cluster of Streptomyces wedmorensis), FomA confer fosfomycin resistance on Escherichia coli [ 3 ]. FomA catalyses phosphorylation of fosfomycin to fosfomycin monophosphate, and FomB phosphorylation of fosfomycin monophosphate to fosfomycin diphosphate, in the presence of ATP and a magnesium ion [ 3 ]. Surprisingly, while FomA homologues are present in many organisms, including fosfomycin-producing ones, no homologues of FomB are detected to date.

FomA and related sequences are members of the Amino Acid Kinase Superfamily (AAK).

1. Characterization of thermophilic archaeal isopentenyl phosphate kinases. Biochemistry 49, 207-17
2. Characterization of the fomA and fomB gene products from Streptomyces wedmorensis, which confer fosfomycin resistance on Escherichia coli. Antimicrob. Agents Chemother. 44, 647-50