4-hydroxybenzoyl-CoA reductase (4-HBCR)

4-hydroxybenzoyl-CoA reductase (4-HBCR) is a specialized molybdenum-containing enzyme found in various anaerobic bacteria and archaea, such as Thauera aromatica and Rhodopseudomonas palustris [1, 6]. It plays a central role in the anaerobic catabolism of aromatic compounds by catalyzing the reductive dehydroxylation of 4-hydroxybenzoyl-CoA to benzoyl-CoA [1, 3]. Structurally, the enzyme is a heterotrimer (αβγ) and a member of the xanthine oxidase family, featuring a molybdenum cofactor, iron-sulfur clusters, and FAD [15, 21]. Unlike typical xanthine oxidases that perform oxidative hydroxylations, 4-HBCR utilizes an inverted electron flow from reduced ferredoxin to achieve its reductive function [19, 21]. While it is not a traditional human therapeutic target, the enzyme is of significant interest in environmental biotechnology for its potential in bioremediation of aromatic pollutants and in microbiome research for its role in processing dietary polyphenols in the gut [17, 30]. The enzyme's unique Birch-like reduction mechanism provides a biological model for the challenging task of breaking down stable aromatic rings in oxygen-free environments [16, 21]. There are currently no FDA-approved drugs or clinical-stage candidates that target this specific enzyme [13, 14].

Other names

4-hydroxybenzoyl-CoA reductase (dehydroxylating)Benzoyl-CoA:acceptor oxidoreductase4-hydroxybenzoyl-CoA:(acceptor) oxidoreductase