Identification and characterization of two families of F420 H2-dependent reductases from Mycobacteria that catalyse aflatoxin degradation.

Abstract:

:Aflatoxins are polyaromatic mycotoxins that contaminate a range of food crops as a result of fungal growth and contribute to serious health problems in the developing world because of their toxicity and mutagenicity. Although relatively resistant to biotic degradation, aflatoxins can be metabolized by certain species of Actinomycetales. However, the enzymatic basis for their breakdown has not been reported until now. We have identified nine Mycobacterium smegmatis enzymes that utilize the deazaflavin cofactor F(420) H(2) to catalyse the reduction of the α,β-unsaturated ester moiety of aflatoxins, activating the molecules for spontaneous hydrolysis and detoxification. These enzymes belong to two previously uncharacterized F(420) H(2) dependent reductase (FDR-A and -B) families that are distantly related to the flavin mononucleotide (FMN) dependent pyridoxamine 5'-phosphate oxidases (PNPOxs). We have solved crystal structures of an enzyme from each FDR family and show that they, like the PNPOxs, adopt a split barrel protein fold, although the FDRs also possess an extended and highly charged F(420) H(2) binding groove. A general role for these enzymes in xenobiotic metabolism is discussed, including the observation that the nitro-reductase Rv3547 from Mycobacterium tuberculosis that is responsible for the activation of bicyclic nitroimidazole prodrugs belongs to the FDR-A family.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Taylor MC,Jackson CJ,Tattersall DB,French N,Peat TS,Newman J,Briggs LJ,Lapalikar GV,Campbell PM,Scott C,Russell RJ,Oakeshott JG

doi

10.1111/j.1365-2958.2010.07356.x

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

561-75

issue

3

eissn

0950-382X

issn

1365-2958

journal_volume

78

pub_type

杂志文章
  • Overexpression and topology of the Shigella flexneri O-antigen polymerase (Rfc/Wzy).

    abstract::Lipopolysaccharides (LPS), particularly the O-antigen component, are one of many virulence determinants necessary for Shigella flexneri pathogenesis. O-antigen biosynthesis is determined mostly by genes located in the rfb region of the chromosome. The rfc/wzy gene encodes the O-antigen polymerase, an integral membrane...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.00884.x

    authors: Daniels C,Vindurampulle C,Morona R

    更新日期:1998-06-01 00:00:00

  • Evidence for the genetic interaction between the actin-binding protein Vrp1 and the RhoGAP Rgd1 mediated through Rho3p and Rho4p in Saccharomyces cerevisiae.

    abstract::The non-essential RGD1 gene from Saccharomyces cerevisiae encodes a protein that has been characterized in vitro as a Rho GTPase activating protein (RhoGAP) for the Rho3 and Rho4 proteins. Rgd1p, which displays a conserved FCH-coiled coil-Rho-GAP domain organization, showed a patch-like distribution in the cell, inclu...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2000.01958.x

    authors: Roumanie O,Peypouquet MF,Bonneu M,Thoraval D,Doignon F,Crouzet M

    更新日期:2000-06-01 00:00:00

  • Regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by the LysR-type regulator LeuO.

    abstract::LeuO is a quiescent LysR-type regulator belonging to the H-NS regulon. Activation of leuO transcription represses expression of pathogenicity island 1 (SPI-1) in Salmonella enterica serovar Typhimurium and inhibits invasion of epithelial cells. Loss of HilE suppresses LeuO-mediated downregulation of SPI-1. Activation ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12500

    authors: Espinosa E,Casadesús J

    更新日期:2014-03-01 00:00:00

  • Purification and functional studies of a potent modified quorum-sensing peptide and a two-peptide bacteriocin in Streptococcus mutans.

    abstract::Bacteria use quorum-sensing signals or autoinducers to communicate. The signals in Gram-positive bacteria are often peptides activated by proteolytic removal of an N-terminal leader sequence. While investigating stimulation of antimicrobial peptide production by the Streptococcus mutans synthetic competence stimulatin...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05312.x

    authors: Petersen FC,Fimland G,Scheie AA

    更新日期:2006-09-01 00:00:00

  • Cis-acting signals controlling translational initiation in the thermophilic archaeon Sulfolobus solfataricus.

    abstract::In this work, we have studied the in vitro translational features of a bicistronic mRNA of the extremely thermophilic Archaeon Sulfolobus solfataricus, with the aim of determining the nature of the cis-acting signals controlling the recognition of the translation initiation sites in the Archaea. We found that the most...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01615.x

    authors: Condò I,Ciammaruconi A,Benelli D,Ruggero D,Londei P

    更新日期:1999-10-01 00:00:00

  • G1 and S phase arrest in Candida albicans induces filamentous growth via distinct mechanisms.

    abstract::Candida albicans is an opportunistic fungal pathogen. In immunocompromised individuals, it can cause bloodstream infections with high mortality rates. The ability to switch between yeast and hyphal morphologies is a critical virulence factor of C. albicans. In response to diverse environmental cues, several signaling ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.14097

    authors: Chen C,Zeng G,Wang Y

    更新日期:2018-10-01 00:00:00

  • Antibiotic-induced ribosomal assembly defects result from changes in the synthesis of ribosomal proteins.

    abstract::Inhibitors of protein synthesis cause defects in the assembly of ribosomal subunits. In response to treatment with the antibiotics erythromycin or chloramphenicol, precursors of both large and small ribosomal subunits accumulate. We have used a pulse-labelling approach to demonstrate that the accumulating subribosomal...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2011.07555.x

    authors: Siibak T,Peil L,Dönhöfer A,Tats A,Remm M,Wilson DN,Tenson T,Remme J

    更新日期:2011-04-01 00:00:00

  • Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production.

    abstract::Malaria transmission requires that the parasites differentiate into gametocytes prior to ingestion by a mosquito during a blood meal. Once in the mosquito midgut the gametocytes emerge from red blood cells (RBCs), fertilize, develop into ookinetes and finally infectious sporozoites. Gamete surface antigen, Pfs230, is ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05284.x

    authors: Eksi S,Czesny B,van Gemert GJ,Sauerwein RW,Eling W,Williamson KC

    更新日期:2006-08-01 00:00:00

  • A bZIP protein from halophilic archaea: structural features and dimer formation of cGvpE from Halobacterium salinarum.

    abstract::The cGvpE protein of Halobacterium salinarum PHH4 has been identified as transcriptional activator for the promoter of the c-gvpA gene encoding the major gas vesicle structural protein cGvpA. Molecular modelling of the carboxy-terminal region of cGvpE suggests that this protein resembles a basic leucine-zipper protein...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.03031.x

    authors: Plösser P,Pfeifer F

    更新日期:2002-07-01 00:00:00

  • An alternative pathway for reduced folate biosynthesis in bacteria and halophilic archaea.

    abstract::Whereas tetrahydrofolate is an essential cofactor in all bacteria, the gene that encodes the enzyme dihydrofolate reductase (DHFR) could not be identified in many of the bacteria whose genomes have been entirely sequenced. In this communication we show that the halophilic archaea Halobacterium salinarum and Haloarcula...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2004.04339.x

    authors: Levin I,Giladi M,Altman-Price N,Ortenberg R,Mevarech M

    更新日期:2004-12-01 00:00:00

  • The Saccharomyces cerevisiae Crs5 Metallothionein metal-binding abilities and its role in the response to zinc overload.

    abstract::Crs5 is a Saccharomyces cerevisiae Metallothionein (MT), non-homologous to the paradigmatic Cu-thionein Cup1. Although considered a secondary copper-resistance agent, we show here that it determines survival under zinc overload in a CUP1-null background. Its overexpression prevents the deleterious effects exhibited by...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05510.x

    authors: Pagani A,Villarreal L,Capdevila M,Atrian S

    更新日期:2007-01-01 00:00:00

  • Liver-specific protein 2: a Plasmodium protein exported to the hepatocyte cytoplasm and required for merozoite formation.

    abstract::The liver stage is the first stage of the malaria parasite that replicates in the vertebrate host. However, little is known about the interplay between the parasite liver stage and its host cell, the hepatocyte. In this study, we identified an exported protein that has a critical role in parasite development in host h...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12083

    authors: Orito Y,Ishino T,Iwanaga S,Kaneko I,Kato T,Menard R,Chinzei Y,Yuda M

    更新日期:2013-01-01 00:00:00

  • Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton.

    abstract::A family of nine Salmonella typhimurium type III secretion effectors with a conserved amino-terminus have been defined. Three family members (SifA, SifB and SseJ) have previously been demonstrated to localize to the Salmonella-containing vacuole and to Salmonella-induced filaments. In contrast, we demonstrate that two...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.t01-1-03456.x

    authors: Miao EA,Brittnacher M,Haraga A,Jeng RL,Welch MD,Miller SI

    更新日期:2003-04-01 00:00:00

  • The Escherichia coli replication inhibitor CspD is subject to growth-regulated degradation by the Lon protease.

    abstract::Post-translational proteolysis-dependent regulation of critical cellular processes is a common feature in bacteria. The Escherichia coli Lon protease is involved in the control of the SOS response, acid tolerance and nutritional deprivation. Moreover, Lon plays a role in the regulation of toxin-antitoxin (TA) systems ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2011.07646.x

    authors: Langklotz S,Narberhaus F

    更新日期:2011-06-01 00:00:00

  • Mutator mutants of Escherichia coli carrying a defect in the DNA polymerase III tau subunit.

    abstract::To investigate the possible role of accessory subunits of Escherichia coli DNA polymerase III holoenzyme (HE) in determining chromosomal replication fidelity, we have investigated the role of the dnaX gene. This gene encodes both the tau and gamma subunits of HE, which play a central role in the organization and funct...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.05011.x

    authors: Pham PT,Zhao W,Schaaper RM

    更新日期:2006-02-01 00:00:00

  • Polyphosphate binds to the principal sigma factor of RNA polymerase during starvation response in Helicobacter pylori.

    abstract::Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stress-responding alternative sigma...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07233.x

    authors: Yang ZX,Zhou YN,Yang Y,Jin DJ

    更新日期:2010-08-01 00:00:00

  • Identification of the pH-inducible, proton-translocating F1F0-ATPase (atpBEFHAGDC) operon of Lactobacillus acidophilus by differential display: gene structure, cloning and characterization.

    abstract::The influence of low pH on inducible gene expression in Lactobacillus acidophilus was investigated by the use of differential display. Logarithmic phase cultures were exposed to pH 3.5 for various intervals, and RNA was isolated and reverse transcribed. The resultant cDNAs were subjected to PCR and the products were r...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01557.x

    authors: Kullen MJ,Klaenhammer TR

    更新日期:1999-09-01 00:00:00

  • Salmonella enterica serotype Typhimurium MisL is an intestinal colonization factor that binds fibronectin.

    abstract::MisL is an autotransporter protein encoded by Salmonella pathogenicity island 3 (SPI3). To investigate the role of MisL in Salmonella enterica serotype Typhimurium (S. Typhimurium) pathogenesis, we characterized its function during infection of mice and identified a host receptor for this adhesin. In a mouse model of ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04666.x

    authors: Dorsey CW,Laarakker MC,Humphries AD,Weening EH,Bäumler AJ

    更新日期:2005-07-01 00:00:00

  • Host processing of branched DNA intermediates is involved in targeted transposition of IS911.

    abstract::A simplified system using bacterial insertion sequence IS911 has been developed to investigate targeted insertion next to DNA sequences resembling IS ends. We show here that these IR-targeted events occur by an unusual mechanism. In the circular IS911 transposition intermediate the two IRs are abutted to form an IR/IR...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03850.x

    authors: Loot C,Turlan C,Chandler M

    更新日期:2004-01-01 00:00:00

  • Probing the active site of mitogillin, a fungal ribotoxin.

    abstract::Fungal ribotoxins, such as mitogillin and the related Aspergillus toxins restrictocin and alpha-sarcin, are highly specific ribonucleases, which inactivate the ribosome enzymatically by cleaving the eukaryotic 28S RNA of the large ribosomal subunit at a single phosphodiester bond. The site of cleavage occurs between G...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.00987.x

    authors: Kao R,Shea JE,Davies J,Holden DW

    更新日期:1998-08-01 00:00:00

  • The rpf gene of Micrococcus luteus encodes an essential secreted growth factor.

    abstract::Micrococcus luteus secretes a small protein called Rpf, which has autocrine and paracrine signalling functions and is required for the resuscitation of dormant cells. Originally isolated from the supernatant of actively growing cultures, Rpf was also detected on the surface of actively growing bacteria. Most molecules...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.03183.x

    authors: Mukamolova GV,Turapov OA,Kazarian K,Telkov M,Kaprelyants AS,Kell DB,Young M

    更新日期:2002-11-01 00:00:00

  • Functional and structural conservation in the mechanosensitive channel MscL implicates elements crucial for mechanosensation.

    abstract::mscL encodes a channel in Escherichia coli that is opened by membrane stretch force, probably serving as an osmotic gauge. Sequences more or less similar to mscL are found in other bacteria, but the degree of conserved function has been unclear. We subcloned and expressed these putative homologues in E. coli and exami...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.00821.x

    authors: Moe PC,Blount P,Kung C

    更新日期:1998-05-01 00:00:00

  • Identification of the core transmembrane complex of the Legionella Dot/Icm type IV secretion system.

    abstract::Type IV secretion systems (T4SS) are utilized by a wide range of Gram negative bacteria to deliver protein and DNA substrates to recipient cells. The best characterized T4SS are the type IVA systems, which exhibit extensive similarity to the Agrobacterium VirB T4SS. In contrast, type IVB secretion systems share almost...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05446.x

    authors: Vincent CD,Friedman JR,Jeong KC,Buford EC,Miller JL,Vogel JP

    更新日期:2006-12-01 00:00:00

  • Activation of a temporally regulated Caulobacter promoter by upstream and downstream sequence elements.

    abstract::The flagellar genes of Caulobacter crescentus are expressed under cell-cycle control. Expression is regulated by both flagellar assembly cues and cell-cycle events. In this paper we define the sequences required for the expression of the flgF operon, a new class of sigma 54 flagellar promoter. This promoter type is ex...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.tb02300.x

    authors: Marques MV,Gober JW

    更新日期:1995-04-01 00:00:00

  • Impact of the unfolded protein response on the pathogenicity of the necrotrophic fungus Alternaria brassicicola.

    abstract::The unfolded protein response (UPR) is an important stress signalling pathway involved in the cellular development and environmental adaptation of fungi. We investigated the importance of the UPR pathway in the pathogenicity of the plant necrotrophic fungus Alternaria brassicicola, which causes black spot disease on a...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07522.x

    authors: Joubert A,Simoneau P,Campion C,Bataillé-Simoneau N,Iacomi-Vasilescu B,Poupard P,François JM,Georgeault S,Sellier E,Guillemette T

    更新日期:2011-03-01 00:00:00

  • The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals.

    abstract::Genes acrAB encode a multidrug efflux pump in Escherichia coli. We have previously reported that transcription of acrAB is increased under general stress conditions (i.e. 4% ethanol, 0.5 M NaCl, and the stationary phase in Luria-Bertani medium). In this study, lacZ transcriptional fusions and an in vitro gel mobility ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1996.357881.x

    authors: Ma D,Alberti M,Lynch C,Nikaido H,Hearst JE

    更新日期:1996-01-01 00:00:00

  • Transcriptional analysis of the divergent cagAB genes encoded by the pathogenicity island of Helicobacter pylori.

    abstract::Helicobacter pylori strains isolated from most patients with peptic ulcer disease and adenocarcinoma express the vacuolating toxin VacA and contain a pathogenicity island named cag. The cag pathogenicity island codes for more than 40 putative proteins with features similar to bacterial secretion systems. One of these ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1997.5831949.x

    authors: Spohn G,Beier D,Rappuoli R,Scarlato V

    更新日期:1997-10-01 00:00:00

  • The sugar-specific outer membrane channel ScrY contains functional characteristics of general diffusion pores and substrate-specific porins.

    abstract::Escherichia coli K-12 strain PS1-28-37 carries the multicopy plasmid pPSO28-37 containing a DNA fragment coding for two of the proteins that enable bacteria to utilize sucrose as sole carbon source. One of the different gene products of the plasmid is the outer membrane protein, ScrY. This protein was isolated and pur...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1991.tb02153.x

    authors: Schülein K,Schmid K,Benzl R

    更新日期:1991-09-01 00:00:00

  • Secondary metabolic gene cluster silencing in Aspergillus nidulans.

    abstract::In contrast to most primary metabolism genes, the genes involved in secondary metabolism and certain nutrient utilization pathways are clustered in fungi. Recently a nuclear protein, LaeA, was found to be required for the transcription of several secondary metabolite gene clusters in Aspergillus nidulans. Here we show...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05330.x

    authors: Bok JW,Noordermeer D,Kale SP,Keller NP

    更新日期:2006-09-01 00:00:00

  • The power of cooperation: Experimental and computational approaches in the functional characterization of bacterial sRNAs.

    abstract::Trans-acting small regulatory RNAs (sRNAs) are key players in the regulation of gene expression in bacteria. There are hundreds of different sRNAs in a typical bacterium, which in contrast to eukaryotic microRNAs are more heterogeneous in length, sequence composition, and secondary structure. The vast majority of sRNA...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/mmi.14420

    authors: Georg J,Lalaouna D,Hou S,Lott SC,Caldelari I,Marzi S,Hess WR,Romby P

    更新日期:2020-03-01 00:00:00