2026/06/19 by Saisuki Putumbaka, Michael P. Thorgersen, Gerrit J. Schut +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Energy · #Metal-Catalyzed Oxygenation Mechanisms #Metalloenzymes and iron-sulfur proteins #Redox biology and oxidative stress
paper · pdf · doi:10.3389/fmicb.2026.1849799
openalex created_date 2026/06/19 · openalex publication_date 2026/06/19 · openalex updated_date 2026/07/23
Tungsten-containing oxidoreductases (WORs) are a diverse family of enzymes with over 4,000 known members that can be subdivided into 92 clades based on the phylogeny of the large pyranopterin cofactor-containing large subunit (WorL). Despite being widespread in Bacteria and Archaea, particularly in members of the human microbiome, only five of the 92 WOR clades contain a WOR with a defined physiological role in cellular metabolism, primarily—but not exclusively—involved in oxidation of various aldehydes. However, this phylogenetic-based organizational system lacks a perspective on the diversity and complexity of WOR enzymes. Herein, we propose a non-phylogenetic classification system for WORs based on predicted subunit composition and electron carrier specificity that provides insight into potential physiological roles. WORs can be divided into five classes that range in complexity and predicted function. The simpler cytoplasmic Class I-III WORs are involved in aldehyde detoxification, a modified glycolysis pathway and cold adaptation. More complex multimeric WORs are proposed to use multiple electron carriers in bifurcating reactions (Class IV) or interact with various respiratory systems via associations with the cell membrane (Class V). We characterized two new WORs, one Class I and one Class V, from the human gut bacterium Cetobacterium somerae , and showed that the former enzyme had aldehyde oxidation activity but the latter did not. By combining phylogenetic information with the new WOR classification system, we can predict structural and functional characteristics of as-yet uncharaterized WORs and identify unique and novel enzymes for future studies.