Engineered Oxalate Decarboxylase Boosts Activity and Stability for Biological Applications

Oxalate decarboxylase
(OxDC) from Bacillus
subtilis is a Mn-dependent hexameric enzyme that converts
oxalate to carbon
dioxide and formate. Recently, OxDC has attracted the interest of
the scientific community due to its biotechnological and medical applications
for the treatment of hyperoxaluria, a group of pathologic conditions
associated with excessive oxalate urinary excretion caused by either
increased endogenous production or increased exogenous absorption.
The fact that OxDC displays optimum pH in the acidic range represents
a big limitation for most biotechnological applications involving
processes occurring at neutral pH, where the activity and stability
of the enzyme are remarkably reduced. Here, through bioinformatics-guided
protein engineering followed by combinatorial mutagenesis and analyses
of activity and thermal stability, we identified a double mutant of
OxDC endowed with enhanced catalytic efficiency and stability under
physiological conditions. The obtained engineered form of OxDC offers
a potential tool for improved intestinal oxalate degradation in hyperoxaluria
patients.