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1.
The lineage-specific, intrinsically disordered N-terminal extension of monothiol glutaredoxin 1 from trypanosomes contains a regulatory region.
Sturlese, M, Manta, B, Bertarello, A, Bonilla, M, Lelli, M, Zambelli, B, Grunberg, K, Mammi, S, Comini, MA, Bellanda, M
Scientific reports. 2018;(1):13716
Abstract
Glutaredoxins (Grx) are small proteins conserved throughout all the kingdoms of life that are engaged in a wide variety of biological processes and share a common thioredoxin-fold. Among them, class II Grx are redox-inactive proteins involved in iron-sulfur (FeS) metabolism. They contain a single thiol group in their active site and use low molecular mass thiols such as glutathione as ligand for binding FeS-clusters. In this study, we investigated molecular aspects of 1CGrx1 from the pathogenic parasite Trypanosoma brucei brucei, a mitochondrial class II Grx that fulfills an indispensable role in vivo. Mitochondrial 1CGrx1 from trypanosomes differs from orthologues in several features including the presence of a parasite-specific N-terminal extension (NTE) whose role has yet to be elucidated. Previously we have solved the structure of a truncated form of 1CGrx1 containing only the conserved glutaredoxin domain but lacking the NTE. Our aim here is to investigate the effect of the NTE on the conformation of the protein. We therefore solved the NMR structure of the full-length protein, which reveals subtle but significant differences with the structure of the NTE-less form. By means of different experimental approaches, the NTE proved to be intrinsically disordered and not involved in the non-redox dependent protein dimerization, as previously suggested. Interestingly, the portion comprising residues 65-76 of the NTE modulates the conformational dynamics of the glutathione-binding pocket, which may play a role in iron-sulfur cluster assembly and delivery. Furthermore, we disclosed that the class II-strictly conserved loop that precedes the active site is critical for stabilizing the protein structure. So far, this represents the first communication of a Grx containing an intrinsically disordered region that defines a new protein subgroup within class II Grx.
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2.
Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase.
Olson, KR, Gao, Y, Arif, F, Arora, K, Patel, S, DeLeon, ER, Sutton, TR, Feelisch, M, Cortese-Krott, MM, Straub, KD
Redox biology. 2018;:74-85
Abstract
Reactive sulfur species (RSS) such as H2S, HS•, H2Sn, (n = 2-7) and HS2•- are chemically similar to H2O and the reactive oxygen species (ROS) HO•, H2O2, O2•- and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved H2S, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (H2S2-H2S5). H2S was concentration- and oxygen-dependently oxidized by 1μM SOD to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50 of approximately 380μM H2S. H2S concentrations > 750μM inhibited SOD oxidation (IC50 = 1.25mM) with complete inhibition when H2S > 1.75mM. Polysulfides were not metabolized by SOD. SOD oxidation preferred dissolved H2S over hydrosulfide anion (HS-), whereas HS- inhibited polysulfide production. In hypoxia, other possible electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and metabisulfite were ineffective. Manganese SOD also catalyzed H2S oxidation to form polysulfides, but did not metabolize polysulfides indicating common attributes of these SODs. These experiments suggest that, unlike the well-known SOD-mediated dismutation of two O2•- to form H2O2 and O2, SOD catalyzes a reaction using H2S and O2 to form persulfide. These can then combine in various ways to form polysulfides and sulfur oxides. It is also possible that H2S (or polysulfides) interact/react with SOD cysteines to affect catalytic activity or to directly contribute to sulfide metabolism. Our studies suggest that H2S metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to regulate RSS and along with catalase may continue to do so in contemporary organisms.
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3.
Assimilation of alternative sulfur sources in fungi.
Linder, T
World journal of microbiology & biotechnology. 2018;(4):51
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Abstract
Fungi are well known for their metabolic versatility, whether it is the degradation of complex organic substrates or the biosynthesis of intricate secondary metabolites. The vast majority of studies concerning fungal metabolic pathways for sulfur assimilation have focused on conventional sources of sulfur such as inorganic sulfur ions and sulfur-containing biomolecules. Less is known about the metabolic pathways involved in the assimilation of so-called "alternative" sulfur sources such as sulfides, sulfoxides, sulfones, sulfonates, sulfate esters and sulfamates. This review summarizes our current knowledge regarding the structural diversity of sulfur compounds assimilated by fungi as well as the biochemistry and genetics of metabolic pathways involved in this process. Shared sequence homology between bacterial and fungal sulfur assimilation genes have lead to the identification of several candidate genes in fungi while other enzyme activities and pathways so far appear to be specific to the fungal kingdom. Increased knowledge of how fungi catabolize this group of compounds will ultimately contribute to a more complete understanding of sulfur cycling in nature as well as the environmental fate of sulfur-containing xenobiotics.
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4.
Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells.
Crooks, DR, Maio, N, Lane, AN, Jarnik, M, Higashi, RM, Haller, RG, Yang, Y, Fan, TW, Linehan, WM, Rouault, TA
The Journal of biological chemistry. 2018;(21):8297-8311
Abstract
Iron-sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant-negative variants of the primary Fe-S biogenesis scaffold protein iron-sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming associated with loss of Fe-S-containing proteins in several major cellular compartments. Using multiple metabolomics platforms, we observed a ∼12-fold increase in intracellular citrate content in Fe-S-deficient cells, a surge that was due to loss of aconitase activity. The excess citrate was generated from glucose-derived acetyl-CoA, and global analysis of cellular lipids revealed that fatty acid biosynthesis increased markedly relative to cellular proliferation rates in Fe-S-deficient cells. We also observed intracellular lipid droplet accumulation in both acutely Fe-S-deficient cells and iron-starved cells. We conclude that deficient Fe-S biogenesis and acute iron deficiency rapidly increase cellular citrate concentrations, leading to fatty acid synthesis and cytosolic lipid droplet formation. Our findings uncover a potential cause of cellular steatosis in nonadipose tissues.
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Molecular regulation of aluminum resistance and sulfur nutrition during root growth.
Alarcón-Poblete, E, Inostroza-Blancheteau, C, Alberdi, M, Rengel, Z, Reyes-Díaz, M
Planta. 2018;(1):27-39
Abstract
Aluminum toxicity and sulfate deprivation both regulate microRNA395 expression, repressing its low-affinity sulfate transporter ( SULTR2;1 ) target. Sulfate deprivation also induces the high-affinity sulfate transporter gene ( SULTR12 ), allowing enhanced sulfate uptake. Few studies about the relationships between sulfate, a plant nutrient, and aluminum, a toxic ion, are available; hence, the molecular and physiological processes underpinning this interaction are poorly understood. The Al-sulfate interaction occurs in acidic soils, whereby relatively high concentrations of trivalent toxic aluminum (Al3+) may hamper root growth, limiting uptake of nutrients, including sulfur (S). On the other side, Al3+ may be detoxified by complexation with sulfate in the acid soil solution as well as in the root-cell vacuoles. In this review, we focus on recent insights into the mechanisms governing plant responses to Al toxicity and its relationship with sulfur nutrition, emphasizing the role of phytohormones, microRNAs, and ion transporters in higher plants. It is known that Al3+ disturbs gene expression and enzymes involved in biosynthesis of S-containing cysteine in root cells. On the other hand, Al3+ may induce ethylene biosynthesis, enhance reactive oxygen species production, alter phytohormone transport, trigger root growth inhibition and promote sulfate uptake under S deficiency. MicroRNA395, regulated by both Al toxicity and sulfate deprivation, represses its low-affinity Sulfate Transporter 2;1 (SULTR2;1) target. In addition, sulfate deprivation induces High Affinity Sulfate Transporters (HAST; SULTR1;2), improving sulfate uptake from low-sulfate soil solutions. Identification of new microRNAs and cloning of their target genes are necessary for a better understanding of the role of molecular regulation of plant resistance to Al stress and sulfate deprivation.
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Biological sulfur oxidation in wastewater treatment: A review of emerging opportunities.
Lin, S, Mackey, HR, Hao, T, Guo, G, van Loosdrecht, MCM, Chen, G
Water research. 2018;:399-415
Abstract
Sulfide prevails in both industrial and municipal waste streams and is one of the most troublesome issues with waste handling. Various technologies and strategies have been developed and used to deal with sulfide for decades, among which biological means make up a considerable portion due to their low operation requirements and flexibility. Sulfur bacteria play a vital role in these biotechnologies. In this article, conventional biological approaches dealing with sulfide and functional microorganisms are systematically reviewed. Linking the sulfur cycle with other nutrient cycles such as nitrogen or phosphorous, and with continued focus of waste remediation by sulfur bacteria, has led to emerging biotechnologies. Furthermore, opportunities for energy harvest and resource recovery based on sulfur bacteria are also discussed. The electroactivity of sulfur bacteria indicates a broad perspective of sulfur-based bioelectrochemical systems in terms of bioelectricity production and bioelectrochemical synthesis. The considerable PHA accumulation, high yield and anoxygenic growth conditions in certain phototrophic sulfur bacteria could provide an interesting alternative for bioplastic production. In this review, new merits of biological sulfide oxidation from a traditional environmental management perspective as well as a waste to resource perspective are presented along with their potential applications.
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The role of sulfate-reducing prokaryotes in the coupling of element biogeochemical cycling.
Bao, P, Li, GX, Sun, GX, Xu, YY, Meharg, AA, Zhu, YG
The Science of the total environment. 2018;:398-408
Abstract
Sulfate-reducing prokaryotes (SRP) represent a diverse group of heterotrophic and autotrophic microorganisms that are ubiquitous in anoxic habitats. In addition to their important role in both sulfur and carbon cycles, SRP are important biotic and abiotic regulators of a variety of sulfur-driven coupled biogeochemical cycling of elements, including: oxygen, nitrogen, chlorine, bromine, iodine and metal(loid)s. SRP gain energy form most of the coupling of element transformation. Once sulfate-reducing conditions are established, sulfide precipitation becomes the predominant abiotic mechanism of metal(loid)s transformation, followed by co-precipitation between metal(loid)s. Anthropogenic contamination, since the industrial revolution, has dramatically disturbed sulfur-driven biogeochemical cycling; making sulfur coupled elements transformation complicated and unpredictable. We hypothesise that sulfur might be detoxication agent for the organic and inorganic toxic compounds, through the metabolic activity of SRP. This review synthesizes the recent advances in the role of SRP in coupled biogeochemical cycling of diverse elements.
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Case Study: Microbial Ecology and Forensics of Chinese Drywall-Elemental Sulfur Disproportionation as Primary Generator of Hydrogen Sulfide.
Tomei Torres, FA
Microbial ecology. 2018;(1):37-48
Abstract
Drywall manufactured in China released foul odors attributed to volatile sulfur compounds. These included hydrogen sulfide, methyl mercaptan, and sulfur dioxide. Given that calcium sulfate is the main component of drywall, one would suspect bacterial reduction of sulfate to sulfide as the primary culprit. However, when the forensics, i.e., the microbial and chemical signatures left in the drywall, are studied, the evidence suggests that, rather than dissimilatory sulfate reduction, disproportionation of elemental sulfur to hydrogen sulfide and sulfate was actually the primary cause of the malodors. Forensic evidence suggests that the transformation of elemental sulfur went through several abiological and microbial stages: (1) partial volatilization of elemental sulfur during the manufacture of plaster of Paris, (2) partial abiotic disproportionation of elemental sulfur to sulfide and thiosulfate during the manufacture of drywall, (3) microbial disproportionation of elemental sulfur to sulfide and sulfate resulting in neutralization of all alkalinity, and acidification below pH 4, (4) acidophilic microbial disproportionation of elemental sulfur to sulfide and sulfuric acid, and (5) hydrogen sulfide volatilization, coating of copper fixtures resulting in corrosion, and oxidation to sulfur dioxide.
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9.
Mathematical modeling of simultaneous carbon-nitrogen-sulfur removal from industrial wastewater.
Xu, XJ, Chen, C, Wang, AJ, Ni, BJ, Guo, WQ, Yuan, Y, Huang, C, Zhou, X, Wu, DH, Lee, DJ, et al
Journal of hazardous materials. 2017;:371-381
Abstract
A mathematical model of carbon, nitrogen and sulfur removal (C-N-S) from industrial wastewater was constructed considering the interactions of sulfate-reducing bacteria (SRB), sulfide-oxidizing bacteria (SOB), nitrate-reducing bacteria (NRB), facultative bacteria (FB), and methane producing archaea (MPA). For the kinetic network, the bioconversion of C-N by heterotrophic denitrifiers (NO3-→NO2-→N2), and that of C-S by SRB (SO42-→S2-) and SOB (S2-→S0) was proposed and calibrated based on batch experimental data. The model closely predicted the profiles of nitrate, nitrite, sulfate, sulfide, lactate, acetate, methane and oxygen under both anaerobic and micro-aerobic conditions. The best-fit kinetic parameters had small 95% confidence regions with mean values approximately at the center. The model was further validated using independent data sets generated under different operating conditions. This work was the first successful mathematical modeling of simultaneous C-N-S removal from industrial wastewater and more importantly, the proposed model was proven feasible to simulate other relevant processes, such as sulfate-reducing, sulfide-oxidizing process (SR-SO) and denitrifying sulfide removal (DSR) process. The model developed is expected to enhance our ability to predict the treatment of carbon-nitrogen-sulfur contaminated industrial wastewater.
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10.
Enzymatic Carbon-Sulfur Bond Formation in Natural Product Biosynthesis.
Dunbar, KL, Scharf, DH, Litomska, A, Hertweck, C
Chemical reviews. 2017;(8):5521-5577
Abstract
Sulfur plays a critical role for the development and maintenance of life on earth, which is reflected by the wealth of primary metabolites, macromolecules, and cofactors bearing this element. Whereas a large body of knowledge has existed for sulfur trafficking in primary metabolism, the secondary metabolism involving sulfur has long been neglected. Yet, diverse sulfur functionalities have a major impact on the biological activities of natural products. Recent research at the genetic, biochemical, and chemical levels has unearthed a broad range of enzymes, sulfur shuttles, and chemical mechanisms for generating carbon-sulfur bonds. This Review will give the first systematic overview on enzymes catalyzing the formation of organosulfur natural products.