Discovery
of a Cyclic Phosphodiesterase That Catalyzes
the Sequential Hydrolysis of Both Ester Bonds to Phosphorus
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Abstract
The
bacterial C–P lyase pathway is responsible for the metabolism
of unactivated organophosphonates under conditions of phosphate starvation.
The cleavage of the C–P bond within ribose-1-methylphosphonate-5-phosphate
to form methane and 5-phospho-ribose-1,2-cyclic phosphate (PRcP) is
catalyzed by the radical SAM enzyme PhnJ. In <i>Escherichia coli</i> the cyclic phosphate product is hydrolyzed to ribose-1,5-bisphosphate
by PhnP. In this study, we describe the discovery and characterization
of an enzyme that can hydrolyze a cyclic phosphodiester directly to
a vicinal diol and inorganic phosphate. With PRcP, this enzyme hydrolyzes
the phosphate ester at carbon-1 of the ribose moiety to form ribose-2,5-bisphosphate,
and then this intermediate is hydrolyzed to ribose-5-phosphate and
inorganic phosphate. Ribose-1,5-bisphosphate is neither an intermediate
nor a substrate for this enzyme. Orthologues of this enzyme are found
in the human pathogens <i>Clostridium difficile</i> and <i>Eggerthella lenta</i>. We propose that this enzyme be called
cyclic phosphate dihydrolase (cPDH) and be designated as PhnPP