Vitamin B₂ Catabolism: Nature's Route from Riboflavin to Acetoacetate and Pyruvate

Here we report the cloning and complete in vitro reconstitution of the enzymes of the riboflavin catabolic pathway. The pathway begins with the oxidative removal of ribose to form lumichrome, which is then solubilized by a P450-catalyzed oxidation of the C7 methyl group, followed by hydrolytic degradation of the C-ring pyrimidine. Loss of C4, in a thiamin-dependent heterocycle decarboxylation, is followed by a xanthine oxidase and Rieske dioxygenase-mediated degradation of the quinoxaline ring. Catechol dioxygenase then catalyzes the conversion of the resulting A-ring-derived catechol to form 4-methyl-6-carboxypyrone. This is cleaved through a hydrolysis/hydration/retroaldol sequence to form pyruvate and acetoacetate, both of which are substrates for the citric acid cycle. The elucidation of the riboflavin catabolic pathway fills an important gap in our understanding of riboflavin metabolism and sets the stage for evaluating the impact of riboflavin catabolism on human and animal nutrition as well as the function of lumichrome as a quorum sensor mimic in the rhizosphere.