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Regulation of iron-sulfur cluster synthesis in Escherichia coli. (A) X-ray structure of an apo-IscR monomer with the proposed Fe-S cluster ligands (C92A, C98A, C104A, and H107) highlighted in red (PDB accession number 4HF1). Note that in this IscR variant, the ligating cysteines have been changed to alanines. (B) X-ray structure of dimeric apo-IscR bound to the hya promoter, which is a type 2 binding site (PDB accession number 4HF1). Each monomer is differently colored (blue and pink). (C) Model for the regulation of ISC and SUF expression in Escherichia coli.
Source publication
Building iron-sulfur (Fe-S) clusters and assembling Fe-S proteins are essential actions for life on Earth. The three processes that sustain life, photosynthesis, nitrogen fixation, and respiration, require Fe-S proteins. Genes coding for Fe-S proteins can be found in nearly every sequenced genome. Fe-S proteins have a wide variety of functions, and...
Contexts in source publication
Context 1
... control. IscR is a TF that belongs to the Rrf2 family of winged helix-turn-helix TFs. It hosts a [2Fe-2S] cluster, which allows sensing aerobiosis, oxidative stress, iron limitation, and, possibly, reactive nitrogen species (RNS). Mutagenesis and structural studies have identified residues Cys92, Cys98, Cys104, and His107 as Fe-S cluster ligands (Fig. 4A) (114,115). A His ligand is uncommon, and this might render the cluster labile and sensitive to stress signals. It is particularly useful for the IscR regulator since its activity is not influenced by the oxidative state of its cluster but is strictly dependent on the presence/absence of the cluster (115,116). IscR is found in the ...
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... for the ISC machinery. Next, apo-IscR accumulates, and this form activates the expression of the suf operon (119). In summation, IscR represses the transcription of isc and activates suf transcription in its Fe-S-bound and unbound forms, respectively, directly connecting both the cell's Fe-S cluster biogenesis capacity and Fe-S cluster demand (Fig. ...
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... suf operon expression (120). Meanwhile, ryhB, which is also repressed by holo-Fur, is expressed and targets the intergenic region between iscR and iscS, causing translation inhibition of the downstream iscSUA genes and probably mRNA decay, whereas a stem-loop structure forms, enabling the stabilization of the upstream iscR messenger moiety (Fig. 4C) (121). Under these conditions, apo-IscR accumulates and activates the expression of the suf operon. Consequently, iron limitation enhances the expression of the suf operon by both alleviating Fur repression and favoring apo-IscR activation, while the expression of iscSUA is shut off by RyhB-mediated translation inhibition and possibly ...
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... Switching the Fe-S cluster synthesis machineries under redox stress. The OxyR transcriptional regulator activates the expression of suf genes in response to H 2 O 2 (Fig. 4C). The OxyR binding site is located far upstream from the sufA promoter (operon sufABCDSE), and OxyR-dependent activation requires the binding activity of IHF to bring the OxyR site closer to the 210 and 235 promoter elements (123). OxyRand apo-IscR-mediated activations have been found to be additive (119). Thus, because oxidative stress ...
Citations
... Cysteine desulfurase (Suf) gene has been documented as an important protein that contributes to the assembly or repair of oxygen-labile iron-sulfur clusters under oxidative stress and could also facilitate iron uptake from extracellular iron chelators under iron limitation [80]. Iron-sulfur clusters which include cysteine desulfurase (suf) remain the oldest, ubiquitous, indispensable, and most versatile inorganic cofactors that are required to sustain fundamental life processes [81,82]. Earlier studies have reported sufB and sufD in Bacillus subtilis [83] and other bacteria such as E. coli [84,85], and Enterococcus faecalis [86], hence, its detection in Bacillus and Klebsiella isolates in this work suggest these genes are essential for the biogenesis of Fe-S cluster in the SufBCD complex [87]. ...
This study explores the potential of some soil bacteria in the synthesis of iron oxide nanoparticles (IONPs), highlighting their advantages in terms of iron uptake and tolerance capacity. Soil samples collected from a metal fabricating workshop were successively screened in nutrient broth containing 1% iron salts (Fe2O3, FeCl3, and FeSO4) following a standard microbiological sampling technique. The recovered bacterial isolates (persister cells) were identified using polymerase chain reaction (PCR) and 16S rRNA sequencing. Ten bacterial isolates identified as Sporosarcina luteola, Bacillus badius (2), Bacillus subtilis (2), Bacillus tropicus, Bacillus cereus, Klebsiella pneumoniae, Klebsiella quasipneumoniae and Klebsiella africana were recovered. The method reports that six of the bacterial isolates extracellularly synthesize IONPs and the result from the energy dispersion x-ray (EDX) spectral analysis indicated varying weight percentages of bio-reduced iron by Bacillus subtilis-A12 (48.59%), Klebsiella quasipneumoniae (39.99%), Bacillus subtilis-B1 (39.97%), Bacillus cereus (38.62%), Bacillus badius (33.79%) and Klebsiella africana (32.61%). The IONPs exhibited absorbance peaks in the range of 250–350 nm, with a mean area size estimated between 31–72 nm using ImageJ software. Additionally, the presence of iron reductase (fhu) and cysteine desulfurase (suf) genes were detected in the recovered Bacillus and Klebsiella species through PCR analysis. This study has provided valuable insights into the physiology and genomic functions essential for microbial synthesis of IONPs and their relevance to nano-bioremediation.
... To alleviate byproduct inhibition, a 5'-methylthioadenosine/S-adenosyl-homocysteine nucleosidase is required for 5'-deoxyadenosine degradation [82]. Additionally, the regeneration of the [2Fe-2S] 2+ cluster by the Isc or Suf iron-sulfur cluster assembly system is another bottleneck issue in biotin synthesis [83,84]. Despite extensive research on the structure and catalytic mechanism of BioB in the four conserved steps of biotin synthesis, there is currently limited exploration aimed at improving its catalytic activity. ...
Biotin, serving as a coenzyme in carboxylation reactions, is a vital nutrient crucial for the natural growth, development, and overall well-being of both humans and animals. Consequently, biotin is widely utilized in various industries, including feed, food, and pharmaceuticals. Despite its potential advantages, the chemical synthesis of biotin for commercial production encounters environmental and safety challenges. The burgeoning field of synthetic biology now allows for the creation of microbial cell factories producing bio-based products, offering a cost-effective alternative to chemical synthesis for biotin production. This review outlines the pathway and regulatory mechanism involved in biotin biosynthesis. Then, the strategies to enhance biotin production through both traditional chemical mutagenesis and advanced metabolic engineering are discussed. Finally, the article explores the limitations and future prospects of microbial biotin production. This comprehensive review not only discusses strategies for biotin enhancement but also provides in-depth insights into systematic metabolic engineering approaches aimed at boosting biotin production.
... The whole genome based phylogenetic analysis showed that strain MHSD_37 was closely related to Bacillus albus strain N35-10-2 T with a digital DNA-DNA hybridization (dDDH) of 58%, which was the highest observed dDDH with a closely related species (Table 2). In contrast the ANI analysis revealed that strain MHSD_37 was closest to B. paranthracis MCCC 1A00395 with a value of 96.2% (Fig. 1), which was above the species boundary value ANI > 95-96% ( Fig. 1) [26]. Moreover, the strain had an ANI value of 95.9 with B. tropicus, which was also above the species boundary value [26]. ...
... In contrast the ANI analysis revealed that strain MHSD_37 was closest to B. paranthracis MCCC 1A00395 with a value of 96.2% (Fig. 1), which was above the species boundary value ANI > 95-96% ( Fig. 1) [26]. Moreover, the strain had an ANI value of 95.9 with B. tropicus, which was also above the species boundary value [26]. On the other hand, the ANI value between strain MHSD_37 and Bacillus albus strain N35-10-2 T was 94.5%. ...
... BEs influence plant growth promotion through mechanisms such as phytohormone modulation, improving plant nutrient availability or uptake, as well as enhancing plant tolerance to stress and toxic heavy metals or hydrocarbons [5]. The role of the Fe-S cluster, encoded by the strain MHSD_37 (Table 4), is electron transfer to the [24][25][26], and thus plays a crucial role in nitrogen fixation. Moreover, the NIF system is responsible for the maturation of nitrogenase [24], an enzyme responsible for nitrogen fixation [27]. ...
Background
Endophytic bacteria possess a range of unique characteristics that enable them to successfully interact with their host and survive in adverse environments. This study employed in silico analysis to identify genes, from Bacillus sp. strain MHSD_37, with potential biotechnological applications.
Results
The strain presented several endophytic lifestyle genes which encode for motility, quorum sensing, stress response, desiccation tolerance and root colonisation. The presence of plant growth promoting genes such as those involved in nitrogen fixation, nitrate assimilation, siderophores synthesis, seed germination and promotion of root nodule symbionts, was detected. Strain MHSD_37 also possessed genes involved in insect virulence and evasion of defence system. The genome analysis also identified the presence of genes involved in heavy metal tolerance, xenobiotic resistance, and the synthesis of siderophores involved in heavy metal tolerance. Furthermore, LC-MS analysis of the excretome identified secondary metabolites with biological activities such as anti-cancer, antimicrobial and applications as surfactants.
Conclusions
Strain MHSD_37 thereby demonstrated potential biotechnological application in bioremediation, biofertilisation and biocontrol. Moreover, the strain presented genes encoding products with potential novel application in bio-nanotechnology and pharmaceuticals.
... The ISC system is the most studied [Fe-S] cluster biogenesis system in Bacteria and Eucaryotes where a mitochondrial version exists [10][11][12]23,24 . From studies in E. coli, it is considered as the housekeeping system, providing [Fe-S] clusters to all cellular proteins under normal conditions. ...
... The SUF system has been mostly studied in E. coli and Salmonella. SUF is considered as the backup system that these enterobacteria use under stressful conditions such as oxidative stress and iron starvation and is responsible of the maturation of most if not all cellular target proteins 11,23,28,29 . In Enterobacteria, the SUF system is made of six proteins, SufABCDSE ( The Cysteine desulfurase first converts a cysteine into an alanine and a persulfur. ...
... The biological functionality of iron is almost entirely dependent upon its incorporation into proteins, either as a mono-or binuclear species, or in a more complex form as part of iron-sulfur clusters or haem groups [18]. A large proportion of internalized iron is housed within inorganic prosthetic groups called iron-sulfur clusters [19]. Iron-sulfur cluster is one of the oldest substances and exists widely in living organisms. ...
The morphology is the consequence of evolution and adaptation. Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5 μm long and 0.5 μm wide. Many shape-related genes have been identified and used in morphology engineering of this bacteria. However, little is known about if specific metabolism and metal irons could modulate bacteria morphology. Here in this study, we discovered filamentous shape change of E. coli cells overexpressing pigeon MagR, a putative magnetoreceptor and extremely conserved iron-sulfur protein. Comparative transcriptomic analysis strongly suggested that the iron metabolism change and iron accumulation due to the overproduction of MagR was the key to the morphological change. This model was further validated, and filamentous morphological change was also achieved by supplement E. coli cells with iron in culture medium or by increase the iron uptake genes such as entB and fepA. Our study extended our understanding of morphology regulation of bacteria, and may also serves as a prototype of morphology engineering by modulating the iron metabolism.
... Further factors involved in redox and disulfide stresses, including CymR, SufA, SufB, and SufC, respectively, are upregulated at different levels in the ∆GO strain (Table 1). CymR is a repressor involved in the metabolism of cysteine [55], whereas SufA-C are scaffold proteins that play essential roles during the synthesis of iron-sulfur clusters [56]. ...
The guanine oxidized (GO) system of Bacillus subtilis, composed of the YtkD (MutT), MutM and MutY proteins, counteracts the cytotoxic and genotoxic effects of the oxidized nucleobase 8-OxoG. Here, we report that in growing B. subtilis cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H2O2) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of B. subtilis to evolve and survive the noxious effects of oxidative stress were dissected. Genetic and biochemical evidence indicated that the synthesis of KatA was exacerbated, in a PerR-independent manner, and the transcriptional coupling repair factor, Mfd, contributed to HPHR and HPM of the ΔGO strain. Moreover, these phenotypes are associated with wider pleiotropic effects, as revealed by a global proteome analysis. The inactivation of the GO system results in the upregulated production of KatA, and it reprograms the synthesis of the proteins involved in distinct types of cellular stress; this has a direct impact on (i) cysteine catabolism, (ii) the synthesis of iron–sulfur clusters, (iii) the reorganization of cell wall architecture, (iv) the activation of AhpC/AhpF-independent organic peroxide resistance, and (v) increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, B. subtilis activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors.
... The biogenesis of nascent Fe-S clusters is a highly energy intensive process that requires multiple proteins. Fe-S cluster proteins are de novo assembled on scaffold protein ISCU [46,[49][50][51][52]. Inorganic sulfur atoms are supplied by the cysteine desulfurase NFS1, which requires ISD11 to stabilize the interaction and the cofactor pyridoxal phosphate [53][54][55]. ...
Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is ligation of the iron-sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. Here we will explore the ways in which the cell utilizes Fe-S clusters to sense the intracellular environment and respond to maintain equilibrium.
... From there, adaptive changes led to the formation of active sites within the protein that were able to accommodate more complex clusters or additionally allowed to recruit other metals. From the abiotic supply of these first clusters, evolution led to enzyme-catalyzed routes towards [FeS] and [FeMetalS] clusters, so that the biotic world gained complete control over their syntheses [102]. ...
... In addition, a theoretical study on the close evolutionary relationship between amino acid metabolism and the availability of selected coenzymes, in particular thiamine pyrophosphate (TPP), a biological latecomer, casts doubt on the primordial role of the rTCA cycle, particularly because it also depends on the availability of TPP (2-oxoglutarate:ferredoxin oxidoreductase and pyruvate: ferredoxin oxidoreductase (PFOR)) and Fe 4 S 4 clusters [54,101]. A way out of these various dilemmas would be to consider a non-cyclic, horseshoe version of the TCA cycle that has prevailed in Elusimicrobium minutum until today [102] (Figure 2, bottom). It contains a reductive (via oxaloacetate) and an oxidative branch (via citrate), while the Wood-Ljungdahl pathway, the only non-cyclic C1 fixation pathway known, would provide acetyl-CoA. ...
The role of evolutionary theory at the origin of life is an extensively debated topic. The origin and early development of life is usually separated into a prebiotic phase and a protocellular phase, ultimately leading to the Last Universal Common Ancestor. Most likely, the Last Universal Common Ancestor was subject to Darwinian evolution, but the question remains to what extent Darwinian evolution applies to the prebiotic and protocellular phases. In this review, we reflect on the current status of evolutionary theory in origins of life research by bringing together philosophy of science, evolutionary biology, and empirical research in the origins field. We explore the various ways in which evolutionary theory has been extended beyond biology; we look at how these extensions apply to the prebiotic development of (proto)metabolism; and we investigate how the terminology from evolutionary theory is currently being employed in state-of-the-art origins of life research. In doing so, we identify some of the current obstacles to an evolutionary account of the origins of life, as well as open up new avenues of research.
... Indeed, when an homologs Fe-S gene was experimentally deleted in Allochromatium vinosum, the sulfur oxidation rates were significantly reduced 71 . These proteins are essential in supporting bacterial life as they are involved in three vital processes such as, photosynthesis, nitrogen fixation and oxidation/respiration, and hydrogen/sulfur metabolism 72,73 . Considering that photosynthesis and nitrogen fixation were absent under RIS 5 , it is reasonable to speculate that this Fe-S cluster proteins boost sulfur metabolism as shown in other sulfur-oxidizing bacterial models 71 . ...
Viruses play an important role in the marine ecosystem. However, our comprehension of viruses inhabiting the dark ocean, and in particular, under the Antarctic Ice Shelves, remains limited. Here, we mine single-cell genomic, transcriptomic, and metagenomic data to uncover the viral diversity, biogeography, activity, and their role as metabolic facilitators of microbes beneath the Ross Ice Shelf. This is the largest Antarctic ice shelf with a major impact on global carbon cycle. The viral community found in the cavity under the ice shelf mainly comprises endemic viruses adapted to polar and mesopelagic environments. The low abundance of genes related to lysogenic lifestyle (<3%) does not support a predominance of the Piggyback-the-Winner hypothesis, consistent with a low-productivity habitat. Our results indicate a viral community actively infecting key ammonium and sulfur-oxidizing chemolithoautotrophs (e.g. Nitrosopumilus spp, Thioglobus spp.), supporting a “kill-the-winner” dynamic. Based on genome analysis, these viruses carry specific auxiliary metabolic genes potentially involved in nitrogen, sulfur, and phosphorus acquisition. Altogether, the viruses under Antarctic ice shelves are putatively involved in programming the metabolism of ecologically relevant microbes that maintain primary production in these chemosynthetically-driven ecosystems, which have a major role in global nutrient cycles.
... Iron-sulfur [Fe-S] clusters are very ancient protein cofactors essential for life and are involved in many biological processes [14,15]. Our taxonomic distribution and evolution of the characterized machineries, SUF and ISC, in Bacteria [16]. ...
Establishing the origin of mitochondria and plastids is key to understand 2 founding events in the origin and early evolution of eukaryotes. Recent advances in the exploration of microbial diversity and in phylogenomics approaches have indicated a deep origin of mitochondria and plastids during the diversification of Alphaproteobacteria and Cyanobacteria , respectively. Here, we strongly support these placements by analyzing the machineries for assembly of iron–sulfur ([Fe–S]) clusters, an essential function in eukaryotic cells that is carried out in mitochondria by the ISC machinery and in plastids by the SUF machinery. We assessed the taxonomic distribution of ISC and SUF in representatives of major eukaryotic supergroups and analyzed the phylogenetic relationships with their prokaryotic homologues. Concatenation datasets of core ISC proteins show an early branching of mitochondria within Alphaproteobacteria , right after the emergence of Magnetococcales . Similar analyses with the SUF machinery place primary plastids as sister to Gloeomargarita within Cyanobacteria . Our results add to the growing evidence of an early emergence of primary organelles and show that the analysis of essential machineries of endosymbiotic origin provide a robust signal to resolve ancient and fundamental steps in eukaryotic evolution.
