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. Uses In 1998 the consumption of phosphonates was 56,000 tons worldwide – 40,000 tons in the US, 15,000 tons in Europe and less than 800 tons in Japan. The demand of phosphonates grows steadily at 3% annually. Metal chelants Since the work of Gerold Schwarzenbach in 1949, phosphonic acids are known as effective chelating agents. The introduction of an amine group into the molecule to obtain −NH2−C−PO(OH)2 increases the metal binding abilities of the phosphonate. Examples for such compounds are NTMP, EDTMP and DTPMP. These phosphonates are the structural analogues to the well-known aminopolycarboxylate such as EDTA. The stability of the metal complexes increases with increasing number of phosphonic acid groups. Phosphonates are highly water-soluble while the phosphonic acids are only sparingly so. Phosphonates are effective chelating agents. That is, they bind tightly to di- and trivalent metal ions, which is useful in water softening. In this way, they prevent formation of insoluble precipitates (scale). The binding of these ligands also suppresses the catalytic properties of metal ions. They are stable under harsh conditions. For these reasons, an important industrial use of phosphonates is in cooling waters, desalination systems, and in oil fields to inhibit scale formation. Phosphonates are also regularly used in reverse osmosis systems as antiscalants. Phosphonates in cooling water systems also serve to control corrosion of iron and steel. In pulp and paper manufacturing and in textile industry they serve as "peroxide bleach stabilizers", by chelating metals that could inactivate the peroxide. In detergents they are used as a combination of chelating agent, scale inhibitor, and bleach stabilizer. Phosphonates are also increasingly used in medicine to treat disorders associated with bone formation and calcium metabolism. Furthermore, they serve