(2-Amino-1-hydroxyethyl)phosphonic acid

Acs Catalysis, 2017:3521-3531.

Mechanism of Organophosphonate Catabolism by Diiron Oxygenase PhnZ: A Third Iron-Mediated O-O Activation Scenario in Nature.[Reference: WebLink]

Diiron oxygenase PhnZ catalyzes the catabolism of organophosphonate (Pn) (R)-2-amino-1-hydroxyethylphosphonic((2-Amino-1-hydroxyethyl)phosphonic acid) to glycine and inorganic phosphate (Pi).
METHODS AND RESULTS:
In this Pn catabolism way, PhnZ oxidatively cleaves the highly stable C-P bond in Pn to produce Pi. However, the mechanism of this enzyme that affords aquatic and marine bacteria in Pi-limited environments to utilize the most abundant environmental Pn (2-amino-ethylphosphonic acid) as the source of Pi, is still unclear. In this work, extensive QM/MM calculations reveal that the mechanism of PhnZ consists of four consecutive steps: (1) Rate-limiting α-H abstraction of Pn by FeIII-superoxo; (2) Formation of FeIIIOOCα peroxide; (3) Concerted O insertion into Cα-P bond of Pn initiated by “inverse” heterolytic O-O cleavage; (4) Phosphate hydrolysis to glycine and Pi. Intriguingly, the enzymatic reaction mechanism of PhnZ for the crucial breakage of the C-P bond is characterized by the “inverse” heterolytic O-O cleavage of FeIIIOOCα intermediate, which renders the distal O atom more oxidative to oxygenate Pn than the homolytic O-O cleavage.
CONCLUSIONS:
In this way, PhnZ adopts a mechanism quite different from the related diiron oxygenase MIOX, with His62 residue playing an important role. This unusual “inverse” heterolytic O-O cleavage mode, apart from the well-known homolytic and “normal” heterolytic ones, constitutes a third iron-mediated O-O activation scenario in nature, which is expected to have its broad occurrence in oxidative transformation involving heteroatoms of sulfur and phosphorus.