C11orf54 catalyzes L-xylulose formation in human metabolism.

ABSTRACT: Excretion of L-xylulose is the hallmark of pentosuria, the fourth of Garrod's inborn errors of metabolism, yet the molecular basis for L-xylulose formation remains unknown. Here, by projecting coevolutionary data for 511,114 orthogroups across 1,929 eukaryotic genomes onto metabolic maps, we screen for unmapped genes in human metabolism. Among these, we show that the DUF1907 domain of C11orf54 catalyzes formation of L-xylulose by establishing a zinc-coordinated Michaelis complex with β-keto-L-gulonate (BKG). The identification of BKG decarboxylase completes the pentose pathway, in which pentose sugars are produced by decarboxylation of nonphosphorylated hexose precursors. The pathway was present in the unicellular ancestor of animals and is conserved in all deuterostomes, in contrast to th

SUBMITTER: Malatesta M 

PROVIDER: S-EPMC12337341 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature