Structure and mechanism of enzymes involved in biosynthesis and breakdown of the phosphonates fosfomycin, dehydrophos, and phosphinothricin

Recent years have seen a rapid increase in the mechanistic and structural information on enzymes that are involved in the biosynthesis and breakdown of naturally occurring phosphonates. This review focuses on these recent developments with an emphasis on those enzymes that have been characterized crystallographically in the past five years, including proteins involved in the biosynthesis of phosphinothricin, fosfomycin, and dehydrophos and proteins involved in resistance mechanisms.

Research highlights
► HEPD converts 2-hydroxyethylphosphonate to formate and hydroxymethylphosphonate.
► The enzyme does not require any input of electrons, only Fe(II) and O2.
► HppE converts 2-hydroxypropylphosphonate to fosfomycin.
► The hydroxyl oxygen ends up in the epoxide of fosfomycin.
► DhpI is a promiscuous phosphonate methyltransferase.
► FosA/B and FosX provide resistance to fosfomycin.