Isolation and identification of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, an unusual cosynthetic factor in streptomycetes, from Streptomyces lincolnensis.

Kuo, Ming-S. T.; Yurek, David A.; Coats, J. H.; Li, Grace P.

doi:10.7164/antibiotics.42.475

Cited by 37 publications

(36 citation statements)

References 6 publications

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“…The substrates known to exchange electrons with F 420 are rather limited in number and include NADP (20,23,34,46,56); methenyl-, methylene-, and methyltetrahydromethanopterin (33,39,43); H 2 (30); formate (50); the coenzyme M-heptanolyl threonine phosphate heterodimer (17); some alcohols (5); and intermediates in the biosynthesis of tetracyclines (41) and lincomycin (8,35).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is a major component in the energy metabolism pathways of methanogenic bacteria and Archaeoglobus fulgidus (5,11,18,19,21,29,32,33), where it participates in a variety of two-electron transfer reactions. It is also found in several Streptomyces species (13), where it is used in the synthesis of tetracyclines (41) and lincomycin (8,35), and in Streptomyces griseus, Scenedesmus acutus, Anacystis nidulans, and methanogens it is a component of the DNA repair enzyme photolyase (22,24,31,40). In Streptomyces species, Archaeoglobus fulgidus, and methanogens it exchanges electrons with NADP via the enzyme NADP-F 420 oxidoreductase (20,23,34,56).…”

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confidence: 99%

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Purification of a novel coenzyme F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis

1996

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A variety of Mycobacterium species contained the 5-deazaflavin coenzyme known as F 420 . Mycobacterium smegmatis was found to have a glucose-6-phosphate dehydrogenase that was dependent on F 420 as an electron acceptor and which did not utilize NAD or NADP. The enzyme was purified by ammonium sulfate fractionation, phenyl-Sepharose column chromatography, F 420 -ether-linked aminohexyl-Sepharose 4B affinity chromatography, and quaternary aminoethyl-Sephadex column chromatography, and the sequence of the first 26 Nterminal amino acids has been determined. The response of enzyme activity to a range of pHs revealed a two-peak pattern, with maxima at pH 5.5 and 8.0. The apparent K m values for F 420 and glucose-6-phosphate were, respectively, 0.004 and 1.6 mM. The apparent native and subunit molecular masses were 78,000 and ϳ40,000 Da, respectively.The electron transfer coenzyme known as F 420 , a 5-deazaflavin, is found in few bacteria. However, it is a major component in the energy metabolism pathways of methanogenic bacteria and Archaeoglobus fulgidus (5,11,18,19,21,29,32,33), where it participates in a variety of two-electron transfer reactions. It is also found in several Streptomyces species (13), where it is used in the synthesis of tetracyclines (41) and lincomycin (8,35), and in Streptomyces griseus, Scenedesmus acutus, Anacystis nidulans, and methanogens it is a component of the DNA repair enzyme photolyase (22,24,31,40). In Streptomyces species, Archaeoglobus fulgidus, and methanogens it exchanges electrons with NADP via the enzyme NADP-F 420 oxidoreductase (20,23,34,56). F 420 is present in Mycobacterium avium (44) and Mycobacterium tuberculosis (13), but in these organisms its metabolic role is unknown. Actually, long before the discovery of F 420 in methanogens, Cousins isolated a yellow pigment from Mycobacterium smegmatis which had a UV-visible spectrum very similar to that of F 420 (9) and Sutton reported on an NADP-like electron transfer component in Mycobacterium phlei (52, 53) which is likely to have been F 420 .Chemical and biochemical properties of F 420 are more similar to those of nicotinamides than to those of flavins, despite its structural resemblance to the latter. Its reduced form is stable for hours in air, it participates in most instances in two-electron transfer reactions, it has a redox potential of Ϫ350 mV, and it reacts rapidly with flavins (29, 54). Figure 1 shows the structure of the monoglutamate form of F 420 found in M. avium (44), but methanogens and others may contain multiglutamate residues.Because of increasing problems in treatment of human disease caused by M. tuberculosis and M. avium infections arising from the global AIDS epidemic, faltering public health systems, and increasing cases of multiple drug resistance in tuberculosis patients (7,25,26,42), we have become interested in examining F 420 -dependent reactions in mycobacteria. Currently, the role of F 420 in mycobacteria and its distribution among different species or strains are unknown. In this study we examine...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Purification of a novel coenzyme F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis

1996

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“…Encoded by the oxytetracycline (oxy), chlorotetracycline (ctc), and dactylocyclinone (dac) gene clusters (29), these enzymes are members of the flavin/deazaflavin oxidoreductase (FDOR) superfamily (30) and utilize F 420 H 2 reduced through the action of Fno (387). F 420 is also required for the synthesis of lincosamide antibiotics by Streptomyces lincolnensis strains (146,388,389), including lincomycin, the precursor of the clinical semisynthetic antibiotic clindamycin (390). On the basis of the accumulation of 4-propylidene-3,4-dihydropyrrole-2-carboxylic acid by strains unable to biosynthesize F 420 , it is proposed that an F 420 H 2 -dependent reductase catalyzes the reduction of the imine moiety of the dihydropyrrole to tetrapyrrole (Fig.…”

Section: Streptomycetesmentioning

confidence: 99%

“…It is assumed that F 420 has a more restricted distribution among bacteria. The cofactor has been identified in representatives of the actinobacterial genera Mycobacterium (23,27,125,145), Streptomyces (25,27,29,146), Nocardia (27,145), and Nocardioides (54). Most of these representatives are saprophytic soil bacteria that adopt a heterotrophic, aerobic lifestyle.…”

Section: Distributionmentioning

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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“…In Archaea, F 420 is required for hydrogenase, formate, methylene-tetrahydromethanopterin, and alcohol dehydrogenases, methylene-tetrahydromethanopterin reductase, and quinone oxidoreductase (20,22,24,28,31,50). F 420 is used by Streptomyces for lincomycin and tetracycline biosynthesis (8,29,34,46), and possibly in mitomycin C biosynthesis (32). The Archaea M. thermoautotrophicum and Halobacterium sp., the green alga Scenedesmus acutus, and the cyanobacterium Synechocystis sp.…”

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Demonstration that fbiC Is Required by Mycobacterium bovis BCG for Coenzyme F ₄₂₀ and FO Biosynthesis

2002

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Using the nitroimidazopyran-based antituberculosis drug PA-824 as a selective agent, transposon-generated Mycobacterium bovis strain BCG (M. bovis) mutants that could not make coenzyme F 420 were identified. Four independent mutants that could not make F 420 or the biosynthesis intermediate FO were examined more closely. These mutants contained transposons inserted in the M. bovis homologue of the Mycobacterium tuberculosis gene Rv1173, which we have named fbiC. Complementation of an M. bovis FbiC ؊ mutant with fbiC restored the F 420 phenotype. These data demonstrate that fbiC is essential for F 420 production and that FbiC participates in a portion of the F 420 biosynthetic pathway between pyrimidinedione and FO. Homologues of fbiC were found in all 11 microorganisms that have been fully sequenced and that are known to make F 420 . Four of these homologues (all from members of the aerobic actinomycetes) coded for proteins homologous over the entire length of the M. bovis FbiC, but in seven microorganisms two separate genes were found to code for proteins homologous with either the N-terminal or C-terminal portions of the M. bovis FbiC. Histidine-tagged FbiC overexpressed in Escherichia coli produced a fusion protein of the molecular mass predicted from the M. bovis BCG sequence (ϳ95,000 Da), as well as three other histidine-tagged proteins of significantly smaller size, which are thought to be proteolysis products of the FbiC fusion protein.The structure of coenzyme F 420 (a 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer agent that is present in few microorganisms) was first determined in studies with the methanogenic Archaea (13,14). This coenzyme had been previously purified from a methanogen, and its spectral and fluorescence properties were described in detail by Cheeseman et al. (6), who gave it its name (for a factor that absorbed maximally in visible wavelengths at 420 nm). However, an earlier report by Cousins described a yellow compound of unknown structure from Mycobacterium smegmatis that, based on its UV-visible spectrum, was almost certainly F 420 (11). Naraoka et al. reported that F 420 was present in Mycobacterium avium (37), and it was subsequently discovered that F 420 was present in Mycobacterium tuberculosis (12) and all other mycobacteria examined (2, 43). Methanobacterium thermoautotrophicum F 420 contains two glutamyl residues (14), but Mycobacterium species contain primarily five-and six-glutamyl forms of F 420 (F 420 -5 and F 420 -6) (2). The structure of F 420 -5 is shown in Fig. 1A.In Mycobacterium and Nocardia species, F 420 is used by F 420 -dependent glucose-6-phosphate dehydrogenase (42,43) and is required for activation of the experimental antituberculosis drug PA-824 by M. tuberculosis and Mycobacterium bovis strain BCG (hereafter referred to as M. bovis) (48). It is likely that other F 420 -dependent reactions will be discovered in mycobacteria, since genes corresponding to several proteins with homology to F 420 -dependent enzymes from other organisms are present in...

show abstract

Isolation and identification of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, an unusual cosynthetic factor in streptomycetes, from Streptomyces lincolnensis.

Cited by 37 publications

References 6 publications

Purification of a novel coenzyme F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis

Purification of a novel coenzyme F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis

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

Demonstration that fbiC Is Required by Mycobacterium bovis BCG for Coenzyme F ₄₂₀ and FO Biosynthesis

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Isolation and identification of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, an unusual cosynthetic factor in streptomycetes, from Streptomyces lincolnensis.

Cited by 37 publications

References 6 publications

Purification of a novel coenzyme F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis

Purification of a novel coenzyme F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis

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

Demonstration that fbiC Is Required by Mycobacterium bovis BCG for Coenzyme F 420 and FO Biosynthesis

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

Demonstration that fbiC Is Required by Mycobacterium bovis BCG for Coenzyme F ₄₂₀ and FO Biosynthesis