SummaryHepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxal 5Ј-phosphate synthases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin-dependent oxidoreductases. F420-dependent members of this family appear to share a common mechanism of hydride transfer from the reduced, low-potential deazaflavin to the electron-deficient ring systems of their substrates.Fifty years ago turkey 'X' disease struck British farms, when fungi growing on groundnuts poisoned nearly 100 000 young turkeys, ducklings and pheasants (Sargeant et al., 1961). The birds' rapid decline and liver pathology spurred the discovery of deadly aflatoxins made by Aspergillus flavus (Bennett and Klich, 2003). Although modern agricultural practices and surveillance have made mycotoxin contamination rare, peanuts, corn, cottonseed and occasionally tree nuts can be infected by Aspergillus spp. (Fig. 1). If infected corn is used for alcoholic fermentation in biofuel plants, mycotoxins could be concentrated in distillers' grain fed to livestock (Wu and Munkvold, 2008); however, aflatoxin levels were generally low in a recent survey of corn co-products (Zhang et al., 2009).Aspergillus flavus and Aspergillus parasiticus produce these furanocoumarin toxins in microsomes through a polyketide biosynthetic pathway requiring more than 20 enzymes (Yabe and Nakajima, 2004). The blue-green fluorescent aflatoxins can be readily detected, yet their environmental fate and mode of degradation are unknown. A new report (Taylor et al., 2010) identified two oxidoreductase protein families from the soil bacterium Mycobacterium smegmatis that initiate aflatoxin breakdown. The key to these enzymes is another fluorescent molecule, coenzyme F 420.Coenzyme F420 is a soluble deazariboflavin cofactor, with a variable lactyl poly-g-glutamate chain, that was probably observed in mycobacteria more than a decade before it was isolated and structurally characterized from methanogenic archaea (Cousins, 1960;Cheeseman et al., 1972). Chemical and genome sequence analyses have identified F420 in many euryarchaea (including all methanogens), one crenarchaeaon (Sulfolobus solfataricus) and several genera of Actinobacteria, including Mycobacterium. In methanogens, F420 mediates two-electron hydride transfer reactions among hydrogenase, methylenetetrahydromethanopterin dehydrogenase and heterodisulfide reductase enzymes, separating the methanogenic reactions from NAD(P) + -dependent biosynthetic reactions. Most bacteria with F420 have an F420-dependent glucose-6-phosphate dehydrogenase enzyme, in addition to the canonical NADP + -dependent enzyme of the pentose phosphate pathway (Purwantini and Daniels, 1996). Concentrations of glucose-6-phosphate were recently found to be much higher in M. smegmatis than in bac...