A systems biology approach to understanding the pathway by which a biogenic organophosphonate is produced during metabolism of 2AEP in S. meliloti 1021

This project involves a systems biology investigation of the gene expression pathway leading to production of a biogenic organophosphonate. Organophosphonates are characterised by a stable, covalent carbon to phosphorus (C-P) bond which gives them resistance to (bio)degradation. The C-P bond mimics the C-O-P bond found in most biological phosphates meaning that a phosphonate molecule can interact with the active site of an enzyme that normally accepts a phosphate group, and inhibit it. Organophosphonates can thus intervene in many biochemical processes and are widely used as herbicides, enzyme inhibitors, antibiotics, and pharmacological agents. Various synthetic organophosphonates find diverse biomedical applications such as bone tissue engineering matrices and in the treatment of HIV and cancer. The increasing use of organophosphonate compounds, coupled with their well-known persistence make it essential that full understanding of the routes by which they are metabolised is achieved.