Phosphoribosyl cyclic phosphodiesterase (PhnP) (PhnP)

Phosphoribosyl cyclic phosphodiesterase (PhnP) is a bacterial enzyme belonging to the metallo-beta-lactamase superfamily that plays an essential role in the carbon-phosphorus (C-P) lyase pathway. This metabolic route allows bacteria, including Escherichia coli and various soil and gut microbes, to utilize organophosphonates as their sole source of phosphorus under phosphate-limited conditions [1, 10]. PhnP specifically catalyzes the regiospecific hydrolysis of the intermediate 5-phospho-alpha-D-ribosyl-1,2-cyclic phosphate into 5-phospho-alpha-D-ribosyl-1-phosphate, which is subsequently converted to the central metabolite PRPP [3, 4]. Due to its vital role in bacterial survival in specific nutrient-poor environments and its absence in humans, PhnP is regarded as a potential target for the development of novel antimicrobial agents [9, 14]. Furthermore, the phn operon containing PhnP has been identified as a factor in bacterial responses and resistance to certain antibiotics, such as fosfomycin, through the regulation of phosphorus-related metabolic stress [13]. Structurally, PhnP functions as a metal-dependent hydrolase, typically requiring manganese ions for its catalytic activity, making its active site a focal point for inhibitor design [1, 7].

Other names

5-phospho-alpha-D-ribosyl-1,2-cyclic phosphate phosphodiesterasePhnP proteinPhosphoribosyl 1,2-cyclic phosphate phosphodiesteraseC-P lyase cyclic phosphodiesterase

PhnP catalyzes the regiospecific hydrolysis of 5-phospho-alpha-D-ribosyl-1,2-cyclic phosphate to 5-phospho-alpha-D-ribosyl-1-phosphate, a key step in the bacterial carbon-phosphorus (C-P) lyase pathway [1, 3].