Sequence–Structure–Function Classification of a Catalytically Diverse Oxidoreductase Superfamily in Mycobacteria

Ahmed, F. Hafna; Carr, P.D.; Lee, Brendon M.; Afriat-Jurnou, Livnat; Mohamed, A. Elaaf; Hong, Nan; Flanagan, Jack U.; Taylor, Matthew C.; Greening, Chris; Jackson, Colin J.

doi:10.1016/j.jmb.2015.09.021

Cited by 80 publications

(280 citation statements)

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“…F 420 is known to serve as a redox cofactor in an increasing number of endogenous processes in mycobacteria, including central carbon metabolism (Bashiri et al, 2008), cell wall modification (Purwantini and Mukhopadhyay, 2013), antioxidant production (Ahmed et al, 2015) and possibly quinone reduction (Gurumurthy et al, 2013). Although the cofactor is synthesized in high levels under oxic conditions (Figure 2), phenotypic evidence suggests it is particularly important for survival under hypoxia (Gurumurthy et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The quality of the models at the global (full protein) and local (F 420 -binding site) scales were assessed using ProQ2 (Ray et al, 2012). F 420 -binding motifs were identified based on previous studies (Eguchi et al, 1984;Purwantini and Daniels, 1998;Aufhammer et al, 2004;Ahmed et al, 2015). …”

Section: Evolutionary Analysismentioning

confidence: 99%

“…Having established that species from the phyla Proteobacteria and Chloroflexi synthesize F 420 , (Greening et al, 2016a) and flavin/deazaflavin oxidoreductases (Ahmed et al, 2015), were also encoded in the three organisms (Supplementary Table S6). Multiple sequence alignments and protein homology models confirmed the residues involved in F 420 binding are almost entirely conserved in these sequences, including residues that interact with the isoalloxazine ring and oligoglutamate chain, that are not found in the flavins FAD and FMN (Supplementary Figure S1).…”

Section: Representatives Of the Proteobacteria And Chloroflexi Synthementioning

confidence: 99%

“…In these organisms, F 420 reduction is coupled to either glucose 6-phosphate or NADPH oxidation and hence is dependent on the pentose phosphate pathway (Greening et al, 2016a). The reduced cofactor (F 420 H 2 ) is reported to enhance the metabolic flexibility of mycobacteria by facilitating the catalysis of a wide range of reductions of endogenous and exogenous organic compounds (Ahmed et al, 2015;Greening et al, 2016a). F 420 also has roles in antibiotic synthesis and xenobiotic degradation in species of Streptomyces (Wang et al, 2013), Rhodococcus (Heiss et al, 2002) and Nocardioides (Ebert et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Our analysis of a protein superfamily, the flavin/ deazaflavin oxidoreductases, identified putative F 420 -utilizing oxidoreductases in microorganisms other than the Euryarchaeota and Actinobacteria, including Chloroflexi, Proteobacteria and Firmicutes (Ahmed et al, 2015). In this work, we explored the distribution of the genes encoding the F 420 biosynthesis enzymes CofC, CofD, CofE, CofG and CofH in public genomes and metagenomes.…”

Section: Introductionmentioning

confidence: 99%

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The methanogenic redox cofactor F420 is widely synthesized by aerobic soil bacteria

et al. 2016

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F 420 is a low-potential redox cofactor that mediates the transformations of a wide range of complex organic compounds. Considered one of the rarest cofactors in biology, F 420 is best known for its role in methanogenesis and has only been chemically identified in two phyla to date, the Euryarchaeota and Actinobacteria. In this work, we show that this cofactor is more widely distributed than previously reported. We detected the genes encoding all five known F 420 biosynthesis enzymes (cofC, cofD, cofE, cofG and cofH) in at least 653 bacterial and 173 archaeal species, including members of the dominant soil phyla Proteobacteria, Chloroflexi and Firmicutes. Metagenome datamining validated that these genes were disproportionately abundant in aerated soils compared with other ecosystems. We confirmed through high-performance liquid chromatography analysis that aerobically grown stationary-phase cultures of three bacterial species, Paracoccus denitrificans, Oligotropha carboxidovorans and Thermomicrobium roseum, synthesized F 420 , with oligoglutamate sidechains of different lengths. To understand the evolution of F 420 biosynthesis, we also analyzed the distribution, phylogeny and genetic organization of the cof genes. Our data suggest that although the F o precursor to F 420 originated in methanogens, F 420 itself was first synthesized in an ancestral actinobacterium. F 420 biosynthesis genes were then disseminated horizontally to archaea and other bacteria. Together, our findings suggest that the cofactor is more significant in aerobic bacterial metabolism and soil ecosystem composition than previously thought. The cofactor may confer several competitive advantages for aerobic soil bacteria by mediating their central metabolic processes and broadening the range of organic compounds they can synthesize, detoxify and mineralize.

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