Molybdoproteomes and evolution of molybdenum utilization.

The trace element molybdenum (Mo) is utilized in many life forms, and it is a key component of several enzymes involved in nitrogen, sulfur, and carbon metabolism. With the exception of nitrogenase, Mo is bound in proteins to a pterin, thus forming the molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. Although a number of molybdoenzymes are well characterized structurally and functionally, evolutionary analyses of Mo utilization are limited. Here, we carried out comparative genomic and phylogenetic analyses to examine the occurrence and evolution of Mo utilization in bacteria, archaea and eukaryotes at the level of (i) Mo transport and Moco utilization trait, and (ii) Mo-dependent enzymes. Our results revealed that most prokaryotes and all higher eukaryotes utilize Mo whereas many unicellular eukaryotes including parasites and most yeasts lost the ability to use this metal. In addition, eukaryotes have fewer molybdoenzyme families than prokaryotes. Dimethylsulfoxide reductase (DMSOR) and sulfite oxidase (SO) families were the most widespread molybdoenzymes in prokaryotes and eukaryotes, respectively. A distant group of the ModABC transport system, was predicted in the hyperthermophilic archaeon Pyrobaculum. ModE-type regulation of Mo uptake occurred in less than 30% of Moco-utilizing organisms. A link between Mo and selenocysteine utilization in prokaryotes was also identified wherein the selenocysteine trait was largely a subset of the Mo trait, presumably due to formate dehydrogenase, a Mo- and selenium-containing protein. Finally, analysis of environmental conditions and organisms that do or do not depend on Mo revealed that host-associated organisms and organisms with low G+C content tend to reduce their Mo utilization. Overall, our data provide new insights into Mo utilization and show its wide occurrence, yet limited use of this metal in individual organisms in all three domains of life.

[1]  K. Rajagopalan.  Molybdenum: an essential trace element in human nutrition. , 1988, Annual review of nutrition.

[2]  J. Reiss,et al.  The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  G. Schwarz,et al.  Structural Basis of Eukaryotic Nitrate Reduction: Crystal Structures of the Nitrate Reductase Active Site , 2005, The Plant Cell Online.

[4]  M. Zahalak,et al.  Molybdate transport and its effect on nitrogen utilization in the cyanobacterium Anabaena variabilis ATCC 29413 , 2004, Molecular microbiology.

[5]  D. Hall,et al.  The high‐resolution crystal structure of the molybdate‐dependent transcriptional regulator (ModE) from Escherichia coli: a novel combination of domain folds , 1999, The EMBO journal.

[6]  Dieter Söll,et al.  The genome of Nanoarchaeum equitans: Insights into early archaeal evolution and derived parasitism , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  V. Gladyshev,et al.  Crystal Structure of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, and an Fe4S4 Cluster , 1997, Science.

[8]  K. Locher,et al.  Structure of an ABC transporter in complex with its binding protein , 2007, Nature.

[9]  K. Shanmugam,et al.  Proposed nomenclature for the genes involved in molybdenum metabolism in Escherichia coli and Saimonella typhimurium , 1992, Molecular microbiology.

[10]  D. Rees,et al.  Crystal Structure of DMSO Reductase: Redox-Linked Changes in Molybdopterin Coordination , 1996, Science.

[11]  M. Penninckx,et al.  An important role for glutathione and gamma-glutamyltranspeptidase in the supply of growth requirements during nitrogen starvation of the yeast Saccharomyces cerevisiae. , 1997, Microbiology.

[12]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[13]  Inna Dubchak,et al.  Reconstruction of regulatory and metabolic pathways in metal-reducing δ-proteobacteria , 2004, Genome Biology.

[14]  K. Shanmugam,et al.  Molybdate transport and regulation in bacteria , 1997, Archives of Microbiology.

[15]  H. Sigel,et al.  Molybdenum and tungsten : their roles in biological processes , 2002 .

[16]  M. Romão,et al.  Molybdenum and tungsten enzymes: the xanthine oxidase family. , 2006, Current opinion in chemical biology.

[17]  K. Rajagopalan.  Novel aspects of the biochemistry of the molybdenum cofactor. , 1991, Advances in enzymology and related areas of molecular biology.

[18]  B. Magasanik,et al.  Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain , 1991, Molecular and cellular biology.

[19]  K. Rajagopalan,et al.  The pterin molybdenum cofactors. , 1992, The Journal of biological chemistry.

[20]  S. Unkles,et al.  Deletion of the cnxE gene encoding the gephyrin-like protein involved in the final stages of molybdenum cofactor biosynthesis in Aspergillus nidulans , 2001, Molecular Genetics and Genomics.

[21]  Inna Dubchak,et al.  Reconstruction Of Regulatory And Metabolic Pathways In Metal-Reducing delta-Proteobacteria , 2004 .

[22]  D. Rees,et al.  Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase , 1995, Science.

[23]  K. Shanmugam,et al.  Global gene expression analysis revealed an unsuspected deo operon under the control of molybdate sensor, ModE protein, in Escherichia coli , 2005, Archives of Microbiology.

[24]  R. Gunsalus,et al.  Functional Dissection of the Molybdate-Responsive Transcription Regulator, ModE, from Escherichia coli , 1998, Journal of bacteriology.

[25]  Biosynthesis of the iron-molybdenum cofactor of nitrogenase. , 1994, Critical reviews in biotechnology.

[26]  L. P. Solomonson,et al.  Model for the regulation of nitrate assimilation , 1977, Nature.

[27]  F. Bittner,et al.  Cell biology of molybdenum. , 2006, Biochimica et biophysica acta.

[28]  O. Gascuel,et al.  A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. , 2003, Systematic biology.

[29]  Antonio Rosato,et al.  A hint to search for metalloproteins in gene banks , 2004, Bioinform..

[30]  R. Mendel,et al.  Molybdenum cofactor biosynthesis and molybdenum enzymes. , 2006, Annual review of plant biology.

[31]  A. Rosato,et al.  Non‐heme iron through the three domains of life , 2007, Proteins.

[32]  M. Delgado,et al.  Functional characterization of the Bradyrhizobium japonicum modA and modB genes involved in molybdenum transport. , 2006, Microbiology.

[33]  N. C. Price,et al.  Characterisation of the molybdenum-responsive ModE regulatory protein and its binding to the promoter region of the modABCD (molybdenum transport) operon of Escherichia coli. , 1997, European journal of biochemistry.

[34]  R. Mendel,et al.  Biosynthesis and molecular biology of the molybdenum cofactor (Moco). , 2002, Metal ions in biological systems.

[35]  Michael Y. Galperin,et al.  The COG database: a tool for genome-scale analysis of protein functions and evolution , 2000, Nucleic Acids Res..

[36]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[37]  H. Schindelin,et al.  A structural comparison of molybdenum cofactor-containing enzymes. , 1998, FEMS microbiology reviews.

[38]  R. Hille.  The Mononuclear Molybdenum Enzymes. , 1997, Chemical reviews.

[39]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[40]  Yan Zhang,et al.  Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues , 2006, Genome Biology.

[41]  K. Shanmugam,et al.  Repression of the Escherichia coli modABCD (molybdate transport) operon by ModE , 1996, Journal of bacteriology.

[42]  G. Barbier,et al.  Purification and biochemical characterization of simplified eukaryotic nitrate reductase expressed in Pichia pastoris. , 2004, Protein expression and purification.

[43]  T. Fujiwara,et al.  An Arabidopsis thaliana high-affinity molybdate transporter required for efficient uptake of molybdate from soil , 2007, Proceedings of the National Academy of Sciences.

[44]  David J Studholme,et al.  A DNA element recognised by the molybdenum-responsive transcription factor ModE is conserved in Proteobacteria, green sulphur bacteria and Archaea , 2003, BMC Microbiology.

[45]  Andrey A Mironov,et al.  Comparative genomics of bacterial zinc regulons: Enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  W. Doolittle,et al.  The nature of the universal ancestor and the evolution of the proteome. , 2000, Current opinion in structural biology.

[48]  D. Rees,et al.  Crystal structure of the molybdate binding protein ModA , 1997, Nature Structural Biology.

[49]  C. G. Young,et al.  Bioinorganic chemistry of pterin-containing molybdenum and tungsten enzymes , 1993 .

[50]  Antonio Rosato,et al.  Zinc through the three domains of life. , 2006, Journal of proteome research.

[51]  B. Snel,et al.  Toward Automatic Reconstruction of a Highly Resolved Tree of Life , 2006, Science.

[52]  D. Rees,et al.  Molybdenum-cofactor-containing enzymes: structure and mechanism. , 1997, Annual review of biochemistry.

[53]  M. Gelfand,et al.  Comparative genomics of regulation of heavy metal resistance in Eubacteria , 2006, BMC Microbiology.

[54]  R. Huber,et al.  Crystal structure of the first dissimilatory nitrate reductase at 1.9 A solved by MAD methods. , 1999, Structure.

[55]  D. Lawson,et al.  Transport, homeostasis, regulation, and binding of molybdate and Tungstate to proteins. , 2002, Metal ions in biological systems.

[56]  W. Hagen,et al.  Tungsten Transport Protein A (WtpA) in Pyrococcus furiosus: the First Member of a New Class of Tungstate and Molybdate Transporters , 2006, Journal of bacteriology.

[57]  A. Wirsing,et al.  Overlapping and Specialized Functions of the Molybdenum-Dependent Regulators MopA and MopB in Rhodobacter capsulatus , 2006, Journal of bacteriology.

[58]  G. Schwarz.  Molybdenum cofactor biosynthesis and deficiency , 2005, Cellular and Molecular Life Sciences CMLS.

[59]  R. Huber,et al.  Crystal structure of dimethyl sulfoxide reductase from Rhodobacter capsulatus at 1.88 A resolution. , 1996, Journal of molecular biology.

[60]  J. Reiss,et al.  Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames. , 1999, American journal of human genetics.

[61]  T. Dierks,et al.  Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency , 1998, Nature Genetics.

[62]  Mikhail S. Gelfand,et al.  Computational Reconstruction of Iron- and Manganese-Responsive Transcriptional Networks in α-Proteobacteria , 2006, PLoS Comput. Biol..

[63]  M. Adams,et al.  Pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon, Pyrococcus furiosus, functions as a CoA-dependent pyruvate decarboxylase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[64]  A. Pich,et al.  Tungstate Uptake by a Highly Specific ABC Transporter inEubacterium acidaminophilum * , 2001, The Journal of Biological Chemistry.