Escherichia coli has a carbon-phosphorus (C-P) lyase with a broad substrate specificity, whose synthesis is induced many hundred fold during phosphate (Pi) limitation. Fourteen genes for phosphonate metabolism comprise the phnC-to-phnP gene cluster: three gene products (PhnC, PhnD, and PhnE) comprise a binding protein-dependent phosphonate transporter, which also transports Pi and phosphate esters; two gene products (PhnF and PhnO) may have a role in gene regulation; and nine gene products (PhnG, PhnH, PhnI, PhnJ, PhnK, PhnL, PhnM, PhnN, and PhnP) may comprise a C-P lyase enzyme complex. Phosphonate biodegradation via a C-P lyase appears to be limited by the specificity of the PhnCDE transporter and not by the specificity of the C-P lyase. These interpretations are based on results from a combination of molecular genetic and molecular biological studies on phosphonate metabolism in E. coli.