Pyruvate:ferredoxin oxidoreductase (PFOR) (PFOR)

Pyruvate:ferredoxin oxidoreductase (PFOR) is a critical enzyme in the anaerobic metabolism of various bacteria and protozoa, where it catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA (UniProt, 2023). Unlike the pyruvate dehydrogenase complex found in aerobic organisms, PFOR utilizes iron-sulfur clusters to transfer electrons to low-potential acceptors such as ferredoxin or flavodoxin (PubMed, PMID: 11585534). This enzyme is essential for the survival of several human pathogens, including Helicobacter pylori, Clostridioides difficile, and Giardia lamblia (NIH, 2022). Because PFOR is absent in human cells, it serves as a highly selective target for antimicrobial therapy (StatPearls, 2023). Drugs such as metronidazole and nitazoxanide act as prodrugs that are reduced by the PFOR system into reactive radical intermediates, which then cause lethal damage to the pathogen's DNA and proteins (PubChem, 2024). However, mutations in the genes encoding PFOR or its associated electron transport proteins are a common mechanism of clinical resistance (Journal of Biological Chemistry, 2021).

Other names

Pyruvate synthasePyruvate:flavodoxin oxidoreductasePyruvate:ferredoxin 2-oxidoreductasePyruvate oxidoreductase

Reductive activation of nitro-group or thiazolide prodrugs into toxic free radicals that cause DNA strand breakage and protein dysfunction.