Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis

Guerra-Lopez, Denise; Daniels, Lacy; Rawat, Mamta

doi:10.1099/mic.0.2006/009241-0

Cited by 45 publications

(50 citation statements)

References 48 publications

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“…The pathway for F 420 biosynthesis has been elucidated and proceeds from two compounds, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and 4-hydroxyphenylpyruvate. These compounds are intermediaries in the biosyntheses of FMN and tyrosine, respectively, and are condensed by F o synthase: two subunits, designated CofG and CofH, are often observed, but these are fused into one protein (FbiC) in mycobacteria (19). The mature cofactor is subsequently produced by two enzymes, CofD (FbiA) and CofE (FbiB).…”

Section: Resultsmentioning

confidence: 99%

Unexpected Abundance of Coenzyme F ₄₂₀ -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

2010

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Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F 420 , which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F 420 biosynthesis nominated many actinobacterial proteins as candidate F 420 -dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F 420 -producing species. The LLM and PPOX families were observed in F 420 -producing species as well as species lacking F 420 but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism's ability to make F 420 allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F 420 -correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F 420 -dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F 420 biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F 420 for its redox reactions. This dependence and the cofactor's rarity may make F 420 -related proteins promising drug targets.

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Section: Resultsmentioning

confidence: 99%

Unexpected Abundance of Coenzyme F ₄₂₀ -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

2010

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“…F 420 H 2 -dependent reductases mediate the biodegradation of nitroaromatic explosives (Ebert et al, 2001), triphenyl dyes (Guerra-Lopez et al, 2007) and furanocoumarins (Taylor et al, 2010), as well as the biosynthesis of tetracycline and pyrrolobenzodiazepine antibiotics Wang et al, 2013). A role for F 420 in equivalent processes seems particularly likely for the Chloroflexi and Tectomicrobia; both phyla contain an abundance of F 420 H 2 -dependent reductases (Supplementary Tables S3 and S6) and are reputed for their biosynthetic versatility and biodegradative capacities (Björnsson et al, 2002;Wilson et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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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“…The observation that F 420 is synthesized even in M. leprae, rendered an unculturable, host-dependent organism through massive genome decay (362), suggests that it has an evolutionarily conserved central role in mycobacterial metabolism. In contrast to methanogens, F 420 is not essential for the viability of mycobacteria under ideal conditions: F 420 biosynthesis (fbiC) and reduction (fgd) genes have been successfully deleted or disrupted in M. smegmatis (28,31,132,363), M. tuberculosis (32,35), and M. bovis (72). However, there is a range of evidence that F 420 contributes to the notorious ability of mycobacteria to persist in deprived and challenging environments (56).…”

Section: Mycobacteriamentioning

confidence: 99%

“…Rhodococcus erythropolis and Nocardia corynebacterioides can also degrade aflatoxin, possibly through using homologous enzymes (472)(473)(474). Environmental mycobacteria are also capable of decolorizing and detoxifying malachite green in an F 420 -dependent manner (132,475); while once extensively used as an antiparasitic in aquaculture, this compound has since become regulated against due to its toxicological properties (476).…”

Section: Bioremediationmentioning

confidence: 99%

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

Greening

Ahmed

Mohamed

et al. 2016

Microbiol Mol Biol Rev

159

208

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SUMMARY5-Deazaflavin cofactors enhance the metabolic flexibility of microorganisms by catalyzing a wide range of challenging enzymatic redox reactions. While structurally similar to riboflavin, 5-deazaflavins have distinctive and biologically useful electrochemical and photochemical properties as a result of the substitution of N-5 of the isoalloxazine ring for a carbon. 8-Hydroxy-5-deazaflavin (Fo) appears to be used for a single function: as a light-harvesting chromophore for DNA photolyases across the three domains of life. In contrast, its oligoglutamyl derivative F420is a taxonomically restricted but functionally versatile cofactor that facilitates many low-potential two-electron redox reactions. It serves as an essential catabolic cofactor in methanogenic, sulfate-reducing, and likely methanotrophic archaea. It also transforms a wide range of exogenous substrates and endogenous metabolites in aerobic actinobacteria, for example mycobacteria and streptomycetes. In this review, we discuss the physiological roles of F420in microorganisms and the biochemistry of the various oxidoreductases that mediate these roles. Particular focus is placed on the central roles of F420in methanogenic archaea in processes such as substrate oxidation, C1pathways, respiration, and oxygen detoxification. We also describe how two F420-dependent oxidoreductase superfamilies mediate many environmentally and medically important reactions in bacteria, including biosynthesis of tetracycline and pyrrolobenzodiazepine antibiotics by streptomycetes, activation of the prodrugs pretomanid and delamanid byMycobacterium tuberculosis, and degradation of environmental contaminants such as picrate, aflatoxin, and malachite green. The biosynthesis pathways of Foand F420are also detailed. We conclude by considering opportunities to exploit deazaflavin-dependent processes in tuberculosis treatment, methane mitigation, bioremediation, and industrial biocatalysis.

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Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis

Cited by 45 publications

References 48 publications

Unexpected Abundance of Coenzyme F ₄₂₀ -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

Unexpected Abundance of Coenzyme F ₄₂₀ -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

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

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

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Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis

Cited by 45 publications

References 48 publications

Unexpected Abundance of Coenzyme F 420 -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

Unexpected Abundance of Coenzyme F 420 -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

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

Physiology, Biochemistry, and Applications of F420- and Fo-Dependent Redox Reactions

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Unexpected Abundance of Coenzyme F ₄₂₀ -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

Unexpected Abundance of Coenzyme F ₄₂₀ -Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions