Microbial Metallomics

Partha Basu

Partha Basu, Professor of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA. Partha Basu earned his PhD in 1991 from Jadavpur University in coordination chemistry under the supervision of Animesh Chakravorty. In 1992, he joined John Enemark at the University of Arizona as a postdoctoral fellow where he worked on the structure-function relationship of a molybdenum enzyme, sulfite oxidase. In 1998, he took a faculty position at Duquesne University, in 2003 he earned his tenure and was promoted to associate professorship, and in 2010 he was promoted to the rank of professor. His research focus is on metals in biology. His particular interests are in bacterial transformation of nitrate and arsenate, development of metal sensors and the coordination chemistry of molybdenum.

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In four short years the journal Metallomics has clearly established itself as a leader in the field of studying diverse aspects of metals in a system, from quantitative speciation, to identification of new metallobiomolecules, to discovering their functions. The field is rapidly maturing so much so that a specialized issue such as this one focusing on Microbial Metallomics is now possible. Since Williams proposed the term ‘metallome’ that describes metal species in a biological system¹, it seems reasonable to coin ‘metallomics’ as the field of investigation of ‘biometals’, as was proposed by Haraguchi². Inclusion of metalloids extends the scope and broadens the field. Three years ago, IUPAC published a technical report on key terminologies of the field³. All of these are indicators of a rapidly maturing subdiscipline.

In a recent editorial of this journal, Maret and Copsey⁴ reminded us that most biochemistry textbooks almost exclusively treat the field from a lens of organic chemists even though organic and inorganic chemistry are almost inseparable in a biological system. A plausible reason may be the inherent challenges of studying metals in biological systems. Even in a simple biological system, such as a bacterial or yeast cell, where significant progress has been made in the field of genomics, studying metal ions remains nontrivial. Many molecules that harbor, or transport metals for a variety of reasons remained unidentified. In a recent article, Cvetkovic et al.⁵ stated that much of microbial metalloproteomes remain uncharacterized. They suggested, “given the major roles that metals have in protein function, native metalloproteomes must be characterized to complement recombinant efforts including structural genomics”. Clearly, genomes do not inform us about the metallome and consequently the function of many metallobiomolecules. Ultimately, understanding their function in an organism at a given time is our quest. We aspire to attain this knowledge, which we hope ultimately will benefit the society whether treating a disease, cleaning up environmental pollutants, or discovering new avenues for energy.

Thus it is seems logical to focus on the metallobiomolecules of simpler organisms, hence this issue on Microbial Metallomics. Microbial metallomics has been important from the context of biogeochemical cycling of elements, to bioremediation, to pathogenesis. The idea of a special issue on Microbial Metallomics was discussed in an editorial board meeting in June of 2011. I discussed the idea with then Deputy Editor, Vibhuti Patel, at the Metals in Biology Gordon Conference in 2012, and soon after the concept of the special issue started to take a shape. In this special issue, there are thirteen articles describing original research or summarizing recent findings. These papers describe the behavior of organisms from arsenic transformation by psychrotolerant bacterium to sulfur metabolism by hyperthermophillic archea, to regulation of copper by pathogenic fungus. The issue has three main foci: structure-function relationships of metalloenzymes, metal homeostasis, and metal containing cofactor acquisition. In addition, it features original contributions describing the effects of mercury in tRNA stability and bioremediation of uranium.

Parey et al. (DOI: 10.1039/c2mt20225e) summarizes dissimilatory sulfate reduction in an archaeal species, Archaeoglobus fulgidus emphasizing the enzymatic structure and mechanism. The findings are compared with the structure based mechanistic details obtained from other sulfate reducing microbes such as Desulfovibrio species. In many of the key enzymes, an iron-sulfur cluster is involved, often in conjunction with another prosthetic group, e.g., heme, siroheme, or FAD. Osborne et al. (DOI:10.1039/c2mt20180a) reports arsenite oxidase from a cold adopted organism Polaromonas sp. str. GM1 that can oxidize arsenite at temperatures below 10 °C. Arsenite oxidases are pterin-containing molybdenum enzymes and this particular enzyme has a higher catalytic activity than that reported for Alcaligenes faecalis, whose crystal structure is known. In their original paper, Kappler and Nouwens (DOI:10.1039/c2mt20230a) discuss the molybdoproteome in a soil bacterium, Starkeya novella, which changes as a function of the growth conditions. Not surprisingly, functions of a large number of the molybdoproteome are not clear, and they are yet to be fully investigated. The review article by Hangasky, (DOI: 10.1039/c3mt20153h) discusses structure-based mechanism of non-heme iron containing α-ketoglutarate oxygenases. These enzymes catalyze a wide variety of reactions from demethylation, to hydroxylation to chlorination to desaturation. These enzymes possess a cupin fold, and effect of the second coordination sphere on the reactivity of the 5 coordinate ferryl species is discussed.

Oglesby-Sherrouse and Murphy (DOI: 10.1039/c3mt20224k) reviewed roles of iron responsive small RNA in cellular physiology and virulence in many bacteria. This small regulatory RNA is produced under iron limiting conditions, which subsequently regulates the expression of iron requiring enzymes, storage proteins and transporters. In pathogenic organisms, the same RNA molecule has been linked with other roles such as motility, biofilm formation, chemotaxicity, and virulence. Luebke et al. (DOI: 10.1039/c3mt20205d) describe the formation of mixed seleno-and tellurotrisulfides by CstR, metalloregulatory protein, from Staphylococcus aureus, a known human pathogen. The di- and trisulfides are stabilized by two cysteine residues; crosslinking of one of them negatively regulates DNA binding, the other showed no effect. The mass spectrometric methodology described in this work may also be applicable to other systems in detecting biologically produced metal clusters, which may help understand their regulation and toxicity. Zinc is an essential element in life as it plays an important role in catalysis, regulation and structure. Zinc homeostasis is achieved by a cohort of transporters, ligands and transcription factors. Wang and Fierke (DOI: 10.1039/c3mt20217h) report that the bacterial adaptive response regulon controls intracellular Zn concentration in E. coli. In particular, under high zinc stress this regulon is more important therefore plays a role in zinc detoxification. Raja et al. (DOI: 10.1039/c3mt20220h) reports copper quota of Cryptococcus neoformans, a pathogen, successfully acquires copper from its environment and internalizes the extra copper without changing its volume. A 50-fold higher concentration of copper in organism isolated from infected mice brain indicates a close relation between the virulence factor with copper requirement. Patterson et al. (DOI: 10.1039/c3mt20241k) reports a Co(II) responsive transcriptional activator in Synechocystis PCC 6803 which regulates the cellular copper concentration. This molecule has lower affinity for Co(II) than the Co(II) affinity of well defined Ni(II) and Zn(II) sensors, binds weakly with DNA, and is only expressed in the presence of Co(II) not the Zn or Ni sensor. This behavior implies an interplay between the Co(II) sensor and vitamin B₁₂ biosynthesis.

Pathogenic organisms such as Streptococcus pneumonia can grow on hemoglobin or heme as a sole source of iron. Romero-Espejel et al. (DOI: 10.1039/c3mt20244e) reported two new hemoglobin and heme binding proteins isolated from S. pneumonia cells grown with hemoglobin or heme as sole iron source. The proteins were isolated by affinity chromatography, and identified by mass spectrometry. Identification of these two new proteins may help explain iron homestasis and its link with pathogenicity. Porphyromonas gingivalis is a leading agent for chronic periodontitis, and heme acquisition is crucial for its survival. The organism acquires heme using different transporters. Wojtowicz et al. (DOI: 10.1039/c3mt20215a) report the binding of several different metal ions to one of the transporters such that it can no longer bind to heme, therefore it may provide a means to reduce the virulence of P. gingivalis.

Hernández (DOI: 10.1039/c3mt20203h) reports degradation of tRNA in Bacillus subtilis in the presence of mercuric chloride. Nearly half of the mercury present in the culture media was taken up by the cells and impacts tRNA metabolism by increasing the shorter tRNA^cys at the expense of mature tRNA^cys, which was repaired subsequently. The latter may be important in understanding oxidative stress. Sousa et al. (DOI: 10.1039/c3mt00052d) report microbial remediation of uranium by Rhodanobacter strain A2-61, through formation of mineral with phosphate. This organism is resistant to uranium and thus may offer a biomineralization means for uranium removal from contaminated sites.

The success of this issue lies with the authors, reviewers and editorial colleagues. I thank the authors for their outstanding contribution underscoring the vibrant field of metallomics. I appreciate the reviewers' unconditional efforts in maintaining a high standard for this journal. Many thanks to May Copsey for her leadership as an editor; Vibhuti Patel and Rebecca Brodie for their tireless work as Deputy Editor and Development Editor, respectively. Lastly to the readers, your interest in this issue highlights the strengths of the field, and I hope this issue will help develop new ideas for the future.

References

1. R. J. P. Williams, Coord. Chem. Rev., 2001, 216, 583–595.
2. H. Haraguchi, J. Anal. At. Spectrom., 2004, 19, 5–14.
3. R. Lobinski, J. S. Becker, H. Haraguchi and B. Sarkar, Pure Appl. Chem., 2010, 82, 493–504.
4. W. Maret and M. Copsey, Metallomics, 2012, 4, 1017–1019.
5. A. Cvetkovic, A. L. Menon, M. P. Thorgersen, J. W. Scott, F. L. Poole II, F. E. Jenney, Jr., W. A. Lancaster, J. L. Praissman, S. Shanmukh, B. J. Vaccaro, S. A. Trauger, E. Kalisiak, J. V. Apon, G. Siuzdak, S. M. Yannone, J. A. Tainer and M. W. W. Adams, Nature, 2010, 466, 779–784.

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