Phosphonates are one of the three sources of phosphate intake in biological cells. The other two are inorganic phosphate and organophosphates.
The naturally occurring phosphonate 2-aminoethylphosphonic acid was first identified in 1959 in plants and many animals, where it is localized in membranes. Phosphonates are quite common among different organisms, from prokaryotes to eubacteria and mushrooms, mollusks, insects and others. They were first reported in natural soils by Newman and Tate (1980). The biological role of the natural phosphonates is still poorly understood. Bis- or polyphosphonates have not been found to occur naturally.
A number of natural product phosphonate substances with antibiotic properties have been identified. Phosphonate natural product antibiotics include fosfomycin which is approved by FDA for the treatment of non-complicated urinary tract infection as well as several pre-clinically investigated substances such as Fosmidomycin (inhibitor isoprenyl synthase), SF-2312 (inhibitor of the glycolytic enzyme enolase, and substances of unknown mode of actions such as alahopcin. Although phosphonates are profoundly cell impermeable, natural product phosphonate antibiotics are effective against a number of organisms, because many bacterial species express glycerol-3-phosphate and glucose-6-phosphate importers, which can be hijacked by phosphonate antibiotics. Fosfomycin resistant bacterial strains frequently have mutations that inactivate these transporters; however, such mutations are not maintained in the absence of antibiotic because of the fitness cost they impose.