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Publication Abstract from PubMed

Despite intensive study, plant lysine catabolism beyond the 2-oxoadipate (2OA) intermediate remains unvalidated. Recently we described a missing step in the D-lysine catabolism of Pseudomonas putida in which 2OA is converted to D-2-hydroxyglutarate (2HG) via hydroxyglutarate synthase (HglS), a DUF1338 family protein. Here we solve the structure of HglS to 1.1 A resolution in substrate-free form and in complex with 2OA. We propose a successive decarboxylation and intramolecular hydroxylation mechanism forming 2HG in a Fe(II)- and O2-dependent manner. Specificity is mediated by a single arginine, highly conserved across most DUF1338 proteins. An Arabidopsis thaliana HglS homolog coexpresses with known lysine catabolism enzymes, and mutants show phenotypes consistent with disrupted lysine catabolism. Structural and biochemical analysis of Oryza sativa homolog FLO7 reveals identical activity to HglS despite low sequence identity. Our results suggest DUF1338-containing enzymes catalyze the same biochemical reaction, exerting the same physiological function across bacteria and eukaryotes.

An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism.,Thompson MG, Blake-Hedges JM, Pereira JH, Hangasky JA, Belcher MS, Moore WM, Barajas JF, Cruz-Morales P, Washington LJ, Haushalter RW, Eiben CB, Liu Y, Skyrud W, Benites VT, Barnum TP, Baidoo EEK, Scheller HV, Marletta MA, Shih PM, Adams PD, Keasling JD Nat Commun. 2020 Jun 10;11(1):2931. doi: 10.1038/s41467-020-16815-3. PMID:32523014^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.