The functional importance of bacterial oxidative phosphonate pathways

Organophosphonates (Pns) are a unique class of natural products characterized by a highly stable C-P bond. Pns exhibit a wide array of interesting structures as well as useful bioactivities ranging from antibacterial to herbicidal. More structurally simple Pns are scavenged and catabolized by bacteria as a source of phosphorus. Despite their environmental and industrial importance, the pathways involved in the metabolism of Pns are far from being fully elucidated. Pathways that have been characterized often reveal unusual chemical transformations and new enzyme mechanisms. Among these, oxidative enzymes play an outstanding role during the biosynthesis and degradation of Pns. They are to a high extent responsible for the structural diversity of Pn secondary metabolites and for the break-down of both man-made and biogenic Pns. Here, we review our current understanding of the importance of oxidative enzymes for microbial Pn metabol-ism, discuss the underlying mechanistic principles, similarities, and differences between pathways. This review illustrates Pn biochemistry to involve a mix of classical redox bio-chemistry and unique oxidative reactions, including ring formations, rearrangements, and desaturations. Many of these reactions are mediated by specialized iron-dependent oxy-genases and oxidases. Such enzymes are the key to both early pathway diversification and late-stage functionalization of complex Pns.

Automated summary

Organophosphonates (Pns) are natural products with a stable C-P bond, exhibiting diverse structures and bioactivities. The metabolism of Pns involves oxidative enzymes, particularly iron-dependent oxygenases and oxidases, which contribute to Pns structural diversity and breakdown. Understanding the importance and mechanisms of these enzymes in microbial Pn metabolism is crucial for early diversification and late-stage functionalization of complex Pns.