Cofactor F-420: an expanded view of its distribution, biosynthesis and roles in bacteria and archaea

Many bacteria and archaea produce the redox cofactor F-420. F-420 is structurally similar to the cofactors FAD and FMN but is catalytically more similar to NAD and NADP. These properties allow F-420 to catalyze challenging redox reactions, including key steps in methanogenesis, antibiotic biosynthesis and xenobiotic biodegradation. In the last 5 years, there has been much progress in understanding its distribution, biosynthesis, role and applications. Whereas F-420 was previously thought to be confined to Actinobacteria and Euryarchaeota, new evidence indicates it is synthesized across the bacterial and archaeal domains, as a result of extensive horizontal and vertical biosynthetic gene transfer. F-420 was thought to be synthesized through one biosynthetic pathway; however, recent advances have revealed variants of this pathway and have resolved their key biosynthetic steps. In parallel, new F-420-dependent biosynthetic and metabolic processes have been discovered. These advances have enabled the heterologous production of F-420 and identified enantioselective F420H2-dependent reductases for biocatalysis. New research has also helped resolve how microorganisms use F-420 to influence human and environmental health, providing opportunities for tuberculosis treatment and methane mitigation. A total of 50 years since its discovery, multiple paradigms associated with F-420 have shifted, and new F-420-dependent organisms and processes continue to be discovered. This review provides a comprehensive description of the distribution and biosynthesis of the redox cofactor F-420, as well as its enzymology, physiological roles and biotechnological applications.

Automated summary

F-420, a redox cofactor produced by many bacteria and archaea, has unique catalytic properties, playing important roles in various redox reactions. Significant progress has been made in understanding its distribution, biosynthesis, function, and applications in recent years.