In Vitro Reconstitution of the Pantothenic Acid Degradation Pathway in Ochrobactrum anthropi

Pantothenic acid is an essential metabolite found throughout all branches of life. Although the enzymes responsible for pantothenic biosynthesis have been characterized, those leading to its biodegradation remain poorly understood. In the study described herein, we showed that use of a “genomic enzymology” strategy enabled identification of four biodegradation pathway genes, which were then confirmed by using kinetic analysis of the purified recombinant enzymes encoded in Ochrobactrum anthropi. The reconstituted pathway converts pantothenic acid to β-alanine and (R)-pantoate, and then (R)-pantoate to aldopentoate, which is transformed to (R)-3,3-dimethylmalate and hence to α-ketoisovalerate. The pathway genes are common to Proteobacterial genomes in which they are not colocated.