Hydrogen cyanide synthase (HCN synthase)

Hydrogen cyanide synthase (HCN synthase) is a membrane-bound enzyme complex, primarily composed of HcnA, HcnB, and HcnC subunits, that catalyzes the oxidative decarboxylation of glycine to generate hydrogen cyanide (HCN) and carbon dioxide. This process, known as cyanogenesis, is a major virulence factor in various pathogenic bacteria, most notably Pseudomonas aeruginosa, which colonizes the respiratory tract of patients with cystic fibrosis. In these settings, biogenically produced HCN acts as a potent toxin that inhibits host mitochondrial respiration by binding to cytochrome c oxidase and facilitates microbial dominance by poisoning competing bacteria such as Staphylococcus aureus. Beyond its role in bacterial virulence, recent research has characterized HCN as a mammalian gasotransmitter produced endogenously to regulate cellular bioenergetics, signal transduction via NMDA receptors, and response to hypoxia. Pathologically elevated HCN production is observed in metabolic conditions like non-ketotic hyperglycinemia, where excessive glycine stimulates cyanogenesis, leading to neurotoxicity. Targeting the HCN synthase complex offers a novel therapeutic approach for anti-virulence strategies, potentially reducing the pathogenicity of multidrug-resistant infections without the strong selective pressure associated with conventional bactericidal antibiotics.

Other names

HcnABC complexGlycine dehydrogenase (cyanide-forming)Cyanide synthaseHydrogen cyanide synthase subunit HcnAHydrogen cyanide synthase subunit HcnBHydrogen cyanide synthase subunit HcnC

Inhibition of the HcnABC enzyme complex to prevent the oxidative decarboxylation of glycine into volatile hydrogen cyanide.