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The Evolutionary Rewiring Of Ubiquitination Targets Has Reprogrammed The Regulation Of Carbon Assimilation In The Pathogenic Yeast Candida Albicans, Doblin Sandai, Zhikang Yin, Laura Selway, David Stead, Janet Walker, Michelle D. Leach, Iryna Bohovych, Iuliana V. Ene, Stavroula Kastora, Susan Budge, Carol A. Munro, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown

Department of Biochemistry: Faculty Publications

Microbes must assimilate carbon to grow and colonize their niches. Transcript profiling has suggested that Candida albicans, a major pathogen of humans, regulates its carbon assimilation in an analogous fashion to the model yeast Saccharomyces cerevisiae, repressing metabolic pathways required for the use of alterative nonpreferred carbon sources when sugars are available. However, we show that there is significant dislocation between the proteome and transcriptome in C. albicans. Glucose triggers the degradation of the ICL1 and PCK1 transcripts in C. albicans, yet isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase (Pck1) are stable and are retained. Indeed, numerous …

Role Of Apoptosis-Inducing Factor, Proline Dehydrogenase, And Nadph Oxidase In Apoptosis And Oxidative Stress, Sathish Kumar Natarajan, Donald F. Becker

Department of Biochemistry: Faculty Publications

Flavoproteins catalyze a variety of reactions utilizing flavin mononucleotide or flavin adenine dinucleotide as cofactors. The oxidoreductase properties of flavoenzymes implicate them in redox homeostasis, oxidative stress, and various cellular processes, including programmed cell death. Here we explore three critical flavoproteins involved in apoptosis and redox signaling, ie, apoptosis-inducing factor (AIF), proline dehydrogenase, and NADPH oxidase. These proteins have diverse biochemical functions and influence apoptotic signaling by unique mechanisms. The role of AIF in apoptotic signaling is two-fold, with AIF changing intracellular location from the inner mitochondrial membrane space to the nucleus upon exposure of cells to apoptotic stimuli. In …

Late-Stage Maturation Of The Rieske Fe/S Protein: Mzm1 Stabilizes Rip1 But Does Not Facilitate Its Translocation By The Aaa Atpase Bcs1, Tie-Zhong Cui, Pamela M. Smith, Jennifer L. Fox, Oleh Khalimonchuk, Dennis R. Winge

Department of Biochemistry: Faculty Publications

The final step in the assembly of the ubiquinol-cytochrome c reductase or bc₁ complex involves the insertion of the Rieske Fe/S cluster protein, Rip1. Maturation of Rip1 occurs within the mitochondrial matrix prior to its translocation across the inner membrane (IM) in a process mediated by the Bcs1 ATPase and subsequent insertion into the bc₁ complex. Here we show that the matrix protein Mzm1 functions as a Rip1 chaperone, stabilizing Rip1 prior to the translocation step. In the absence of Mzm1, Rip1 is prone to either proteolytic degradation or temperature-induced aggregation. A series of Rip1 truncations were engineered …

Substrate Channeling In Proline Metabolism, Benjamin W. Arentson, Nikhilesh Sanyal, Donald F. Becker

Department of Biochemistry: Faculty Publications

Proline metabolism is an important pathway that has relevance in several cellular functions such as redox balance, apoptosis, and cell survival. Results from different groups have indicated that substrate channeling of proline metabolic intermediates may be a critical mechanism. One intermediate is pyrroline-5-carboxylate (P5C), which upon hydrolysis opens to glutamic semialdehyde (GSA). Recent structural and kinetic evidence indicate substrate channeling of P5C/ GSA occurs in the proline catabolic pathway between the proline dehydrogenase and P5C dehydrogenase active sites of bifunctional proline utilization A (PutA). Substrate channeling in PutA is proposed to facilitate the hydrolysis of P5C to GSA which is …

Glutaredoxin 1 Protects Dopaminergic Cells By Increased Protein Glutathionylation In Experimental Parkinson's Disease, Humberto Rodriguez-Rocha, Aracely Garcia Garcia, Laura Zavala-Flores, Sumin Li, Nandakumar Madayiputhiya, Rodrigo Franco

Department of Biochemistry: Faculty Publications

Aims: Chronic exposure to environmental toxicants, such as paraquat, has been suggested as a risk factor for Parkinson's disease (PD). Although dopaminergic cell death in PD is associated with oxidative damage, the molecular mechanisms involved remain elusive. Glutaredoxins (GRXs) utilize the reducing power of glutathione to modulate redox-dependent signaling pathways by protein glutathionylation. We aimed to determine the role of GRX1 and protein glutathionylation in dopaminergic cell death. Results: In dopaminergic cells, toxicity induced by paraquat or 6-hydroxydopamine (6-OHDA) was inhibited by GRX1 overexpression, while its knock-down sensitized cells to paraquat-induced cell death. Dopaminergic cell death was paralleled by protein …

Ergodic Sets As Cell Phenotype Of Budding Yeast Cell Cycle, Robert G. Todd, Tomáš Helikar

Department of Biochemistry: Faculty Publications

It has been suggested that irreducible sets of states in Probabilistic Boolean Networks correspond to cellular phenotype. In this study, we identify such sets of states for each phase of the budding yeast cell cycle. We find that these ‘‘ergodic sets’’ underly the cyclin activity levels during each phase of the cell cycle. Our results compare to the observations made in several laboratory experiments as well as the results of differential equation models. Dynamical studies of this model: (i) indicate that under stochastic external signals the continuous oscillating waves of cyclin activity and the opposing waves of CKIs …

The Cell Collective: Toward An Open And Collaborative Approach To Systems Biology, Tomáš Helikar, Bryan Kowal, Sean Mcclenathan, Mitchell Bruckner, Thaine Rowley, Alex Madrahimov, Ben Wicks, Manish Shrestha, Kahani Limbu, Jim A. Rogers

Department of Biochemistry: Faculty Publications

Background: Despite decades of new discoveries in biomedical research, the overwhelming complexity of cells has been a significant barrier to a fundamental understanding of how cells work as a whole. As such, the holistic study of biochemical pathways requires computer modeling. Due to the complexity of cells, it is not feasible for one person or group to model the cell in its entirety.

Results: The Cell Collective is a platform that allows the world-wide scientific community to create these models collectively. Its interface enables users to build and use models without specifying any mathematical equations or computer code - addressing …

A Framework Genetic Map For Miscanthus Sinensis From Rnaseq-Based Markers Shows Recent Tetraploidy, Kankshita Swaminathan, Won Byoung Chae, Therese Mitros, Kranthi Varala, Liang Xie, Adam Barling, Katarzyna Glowacka, Megan Hall, Stanislaw Jezowski, Ray Ming, Matthew Hudson, John A. Juvik, Daniel S. Rokhsar, Stephen P. Moose

Department of Biochemistry: Faculty Publications

Background: Miscanthus (subtribe Saccharinae, tribe Andropogoneae, family Poaceae) is a genus of temperate perennial C4 grasses whose high biomass production makes it, along with its close relatives sugarcane and sorghum, attractive as a biofuel feedstock. The base chromosome number of Miscanthus (x = 19) is different from that of other Saccharinae and approximately twice that of the related Sorghum bicolor (x = 10), suggesting largescale duplications may have occurred in recent ancestors of Miscanthus. Owing to the complexity of the Miscanthus genome and the complications of self-incompatibility, a complete genetic map with a high density of markers has not …

Concatenation And Concordance In The Reconstruction Of Mouse Lemur Phylogeny: An Empirical Demonstration Of The Effect Of Allele Sampling In Phylogenetics, David W. Weisrock, Stacey Dewitt Smith, Lauren M. Chan, Karla Biebouw, Peter M. Kappeler, Anne D. Yoder

School of Biological Sciences: Faculty Publications

The systematics and speciation literature is rich with discussion relating to the potential for gene tree/species tree discordance. Numerous mechanisms have been proposed to generate discordance, including differential selection, longbranch attraction, gene duplication, genetic introgression, and/or incomplete lineage sorting. For speciose clades in which divergence has occurred recently and rapidly, recovering the true species tree can be particularly problematic due to incomplete lineage sorting. Unfortunately, the availability of multilocus or “phylogenomic” data sets does not simply solve the problem, particularly when the data are analyzed with standard concatenation techniques. In our study, we conduct a phylogenetic study for a nearly …

Draft Genome Sequence Of The Anaerobic, Nitrate-Dependent, Fe(Ii)-Oxidizing Bacterium Pseudogulbenkiania Ferrooxidans Strain 2002, Kathryne G. Byrne-Bailey, Karrie A. Weber, John D. Coates

School of Biological Sciences: Faculty Publications

Pseudogulbenkiania ferrooxidans strain 2002 was isolated as a lithoautotrophic, Fe(II)-oxidizing, nitrate-reducing bacterium. Phylogenetically, it is in a clade within the family Neisseriaceae in the order Nessieriales of the class Betaproteobacteria. It is anticipated that comparative genomic analysis of this strain with other nitrate-dependent, Fe(II)-oxidizing bacteria will aid in the elucidation of the genetics and biochemistry underlying this critically important geochemical metabolism.

Reducing Odorous Voc Emissions From Swine Manure Using Soybean Peroxidase And Peroxides, David B. Parker, Lingshuang Cai, Ki-Hyun Kim, Kristin E. Hales, Mindy J. Spiehs, Bryan L. Woodbury, Audrey L. Atkin, Kenneth Nickerson, Krista D. Patefield

School of Biological Sciences: Faculty Publications

The objective of the research was to determine the optimum application rates of soybean peroxidase (SBP) plus peroxide (SBPP) for reducing odorous VOC emissions from swine manure. Industrial-grade SBP was applied in combination with liquid hydrogen peroxide (H₂O₂) or powdered calcium peroxide (CaO₂) to standard phenolic solutions and swine manure, and emissions were measured in a wind tunnel. The primary odorant in the untreated manure was 4-methylphenol, which accounted for 68–81% of the odor activity value. At the optimum application rate of SBPP (50 g L^-1), 4-methylphenol emissions were reduced from the …

A Social Network Perspective On Measurements Of Dominance Hierarchies, Daizaburo Shizuka, David B. Mcdonald

School of Biological Sciences: Faculty Publications

The hierarchical organization of dominance relations among animals has wide-ranging implications in social evolution. The structure of dominance relations has often been measured using indices of linearity (e.g. Landau’s h, Kendall’s K): the degree to which dominance relations adhere to a linear hierarchy. An alternative measure is the transitivity of dominance relations among sets of three players that all interact with each other, a measure we call triangle transitivity (t_tri). Triangle transitivity and linearity are essentially equivalent when dominance relations of all dyads are known, but such complete observations are rare in empirical studies. Triangle transitivity …

Comparative Transitive And Temporal Orderliness In Dominance Networks, David Mcdonald, Daizaburo Shizuka

School of Biological Sciences: Faculty Publications

Dominance is a social relation between a subordinate animal and the dominant to which it submits. Animal groups seem regularly to form dominance hierarchies in which dominance relations are transitive and stable, but comparative studies are rare. Dominance hierarchies can be formalized as social networks, with arrows (directed edges) pointing from dominant animals (nodes) to subordinates. Using this network perspective, we explored the orderliness of 40 published datasets for taxa from ants to elephants. To quantify orderliness, we used the triad census, a technique from sociology, that enumerates the proportion of orderly (transitive) triads (e.g., A dominates B and C, …

Family Dynamics Through Time: Brood Reduction Followed By Parental Compensation With Aggression And Favoritism, Daizaburo Shizuka, Bruce E. Lyon

School of Biological Sciences: Faculty Publications

Parental food allocation in birds has long been a focal point for life history and parent–offspring conflict theories. In asynchronously hatching species, parents are thought to either adjust brood size through death of marginal offspring (brood reduction), or feed the disadvantaged chicks to reduce the competitive hierarchy (parental compensation). Here, we show that parent American coots (Fulica americana) practice both strategies by switching from brood reduction to compensation across time. Late-hatching chicks suffer higher mortality only for the first few days after hatching. Later, parents begin to exhibit parental aggression towards older chicks and each parent favors a …

Eavesdropping Parasitoids Do Not Cause The Evolution Of Less Conspicuous Signaling Behavior In A Field Cricket, Oliver M. Beckers, William E. Wagner

School of Biological Sciences: Faculty Publications

Males of many species produce conspicuous mating signals to attract females, but these signals can also attract eavesdropping predators and parasites. Males are thus expected to evolve signaling behaviors that balance the sexual selection benefits and the natural selection costs. In the variable field cricket, Gryllus lineaticeps, males sing to attract females, but these songs also attract the lethal parasitoid fly Ormia ochracea. The flies use male crickets as hosts for their larvae, primarily search for hosts during a 2 h period following sunset and prefer the same song types as female crickets. We tested whether males from high-risk populations …

L1pred: A Sequence-Based Prediction Tool For Catalytic Residues In Enzymes With The L1-Logreg Classifier, Yongchao Dou, Jun Wang, Jialiang Yang, Chi Zhang

School of Biological Sciences: Faculty Publications

To understand enzyme functions, identifying the catalytic residues is a usual first step. Moreover, knowledge about catalytic residues is also useful for protein engineering and drug-design. However, to experimentally identify catalytic residues remains challenging for reasons of time and cost. Therefore, computational methods have been explored to predict catalytic residues. Here, we developed a new algorithm, L1pred, for catalytic residue prediction, by using the L1-logreg classifier to integrate eight sequence-based scoring functions. We tested L1pred and compared it against several existing sequence-based methods on carefully designed datasets Data604 and Data63. With ten-fold cross-validation, L1pred showed the area under precision-recall curve …

Covariation Between Understorey Light Environments And Soil Resources In Bornean Mixed Dipterocarp Rain Forest, Sabrina E. Russo, Lin Zhang, Sylvester Tan

School of Biological Sciences: Faculty Publications

Variation in understorey irradiance is both a cause and consequence of the structure and dynamics of closed-canopy forests, which are also influenced by soil nutrients and water availability. We tested the hypothesis that understorey light regimes differ among four mixed dipterocarp forest types that share the same rainfall, but grow on different soils along an edaphic gradient at one site in Borneo. Based on data from photosynthetically active radiation sensors deployed at 1-m height at 36 locations for 351 sensor-days, we found significant soil-related variation in irradiance. The more productive forest types on clay and fine loam had lower daily …

Bacterial Community Structure Of Contrasting Soils Underlying Bornean Rain Forests: Inferences From Microarray And Next-Generation Sequencing Methods, Sabrina E. Russo, Ryan Legge, Karrie A. Weber, Eoin L. Brodie, Katherine C. Goldfarb, Andrew K. Benson, Sylvester Tan

School of Biological Sciences: Faculty Publications

Soil microbial diversity is vast, and we lack even basic understanding of how this diversity is distributed ecologically. Using pyrosequencing and microarray methods, we quantified the structure of bacterial communities in two contrasting soils underlying Bornean rain forest (clay and sandy loam) that differ markedly in soil properties, aboveground tree flora, and leaf litter decomposition rates. We found significant soil-related taxonomic and phylogenetic differences between communities that, due to their proximity, are independent of climate. Bacterial communities showed distinct compositional and taxon-abundance distributions that were significantly correlated with the structure of the overlying tree community. Richness of bacteria was greater …

Insect Herbivory And Propagule Pressure Influence Cirsium Vulgare Invasiveness Across The Landscape, James O. Eckberg, Brigitte Tenhumberg, Svata M. Louda

School of Biological Sciences: Faculty Publications

A current challenge in ecology is to better understand the magnitude, variation, and interaction in the factors that limit the invasiveness of exotic species. We conducted a factorial experiment involving herbivore manipulation (insecticide-in-water vs. water-only control) and seven densities of introduced nonnative Cirsium vulgare (bull thistle) seed. The experiment was repeated with two seed cohorts at eight grassland sites uninvaded by C. vulgare in the central Great Plains, USA. Herbivory by native insects significantly reduced thistle seedling density, causing the largest reductions in density at the highest propagule inputs. The magnitude of this herbivore effect varied widely among sites and …

Larval Performance And Kill Rate Of Convergent Ladybird Beetles, Hippodamia Convergens, On Black Bean Aphids, Aphis Fabae, And Pea Aphids, Acyrthosiphon Pisum, Travis M. Hinkelman, Brigitte Tenhumberg

School of Biological Sciences: Faculty Publications

Generalist predator guilds play a prominent role in structuring insect communities and can contribute to limiting population sizes of insect pest species. A consequence of dietary breadth, particularly in predatory insects, is the inclusion of low-quality, or even toxic, prey items in the predator’s diet. Consumption of low-quality prey items reduces growth, development, and survival of predator larvae, thereby reducing the population sizes of generalist predators. The objective of this paper was to examine the effect of a suspected low-quality aphid species, Aphis fabae (Scopoli) (Hemiptera: Aphididae), on the larval performance of an abundant North American predator, Hippodamia convergens (Guérin-Méneville) …

Evolution Of The Pwwp-Domain Encoding Genes In The Plant And Animal Lineages, Raul Alvarez-Venegas, Zoya Avramova

School of Biological Sciences: Faculty Publications

Background: Conserved domains are recognized as the building blocks of eukaryotic proteins. Domains showing a tendency to occur in diverse combinations (‘promiscuous’ domains) are involved in versatile architectures in proteins with different functions. Current models, based on global-level analyses of domain combinations in multiple genomes, have suggested that the propensity of some domains to associate with other domains in high-level architectures increases with organismal complexity. Alternative models using domain-based phylogenetic trees propose that domains have become promiscuous independently in different lineages through convergent evolution and are, thus, random with no functional or structural preferences. Here we test whether complex protein …

Viscoelastic Properties Of Cell Walls Of Single Living Plant Cells Determined By Dynamic Nanoindentation, Céline M. Hayot, Elham Forouzesh, Ashwani Goel, Zoya Avramova, Joseph A. Turner

School of Biological Sciences: Faculty Publications

Plant development results from controlled cell divisions, structural modifications, and reorganizations of the cell wall. Thereby, regulation of cell wall behaviour takes place at multiple length scales involving compositional and architectural aspects in addition to various developmental and/or environmental factors. The physical properties of the primary wall are largely determined by the nature of the complex polymer network, which exhibits timedependent behaviour representative of viscoelastic materials. Here, a dynamic nanoindentation technique is used to measure the time-dependent response and the viscoelastic behaviour of the cell wall in single living cells at a micron or sub-micron scale. With this approach, significant …

Atx1-Generated H3k4me3 Is Required For Efficient Elongation Of Transcription, Not Initiation, At Atx1- Regulated Genes, Yong Ding, Ivan Ndamukong, Zaoshi Xu, Hanna Lapko, Michael E. Fromm, Zoya Avramova

School of Biological Sciences: Faculty Publications

Tri-methylated H3 lysine 4 (H3K4me3) is associated with transcriptionally active genes, but its function in the transcription process is still unclear. Point mutations in the catalytic domain of ATX1 (ARABIDOPSIS TRITHORAX1), a H3K4 methyltransferase, and RNAi knockdowns of subunits of the AtCOMPASS–like (Arabidopsis Complex Proteins Associated with Set) were used to address this question. We demonstrate that both ATX1 and AtCOMPASS–like are required for high level accumulation of TBP (TATA-binding protein) and Pol II at promoters and that this requirement is independent of the catalytic histone modifying activity. However, the catalytic function is critically required for transcription as H3K4me3 levels …

Sex Allocation In California Oaks: Trade-Offs Or Resource Tracking?, Johannes Knops, Walter D. Koenig

School of Biological Sciences: Faculty Publications

Trade-offs in sex resource allocation are commonly inferred from a negative correlation between male and female reproduction. We found that for three California oak species, aboveground annual net productivity (ANP) differences among individuals were primarily correlated with water availability and soil fertility. Reproductive biomass increased with ANP, but the relative allocation to reproduction was constant, indicating that reproduction tracked productivity, which in turn tracked site quality. Although there was a negative correlation between male and female reproduction, this was not the result of a resource investment trade-off, but rather a byproduct of the positive correlation between female reproductive biomass and …

Urea Amidolyase (Dur1,2) Contributes To Virulence And Kidney Pathogenesis Of Candida Albicans, Dhammika H. M. L. P Navarathna, Michail S. Lionakis, Martin J. Lizak, Jeeva Munasinghe, Kenneth W. Nickerson, David D. Roberts

School of Biological Sciences: Faculty Publications

The intracellular enzyme urea amidolyase (Dur1,2p) enables C. albicans to utilize urea as a sole nitrogen source. Because deletion of the DUR1,2 gene reduces survival of C. albicans co-cultured with a murine macrophage cell line, we investigated the role of Dur1,2p in pathogenesis using a mouse model of disseminated candidiasis. A dur1,2Δ/dur1,2Δ strain was significantly less virulent than the wild-type strain, showing significantly higher survival rate, better renal function, and decreased and less sustained fungal colonization in kidney and brain. Complementation of the mutant restored virulence. DUR1,2 deletion resulted in a milder host inflammatory reaction. Immunohistochemistry, flow …

Svmtrip: A Method To Predict Antigenic Epitopes Using Support Vector Machine To Integrate Tri-Peptide Similarity And Propensity, Bo Yao, Lin Zhang, Shide Liang, Chi Zhang

School of Biological Sciences: Faculty Publications

Identifying protein surface regions preferentially recognizable by antibodies (antigenic epitopes) is at the heart of new immuno-diagnostic reagent discovery and vaccine design, and computational methods for antigenic epitope prediction provide crucial means to serve this purpose. Many linear B-cell epitope prediction methods were developed, such as BepiPred, ABCPred, AAP, BCPred, BayesB, BEOracle/BROracle, and BEST, towards this goal. However, effective immunological research demands more robust performance of the prediction method than what the current algorithms could provide. In this work, a new method to predict linear antigenic epitopes is developed; Support Vector Machine has been utilized by combining the Tri-peptide similarity …

Template-Based Structure Prediction And Classification Of Transcription Factors In Arabidopsis Thaliana, Tao Lu, Yuedong Yang, Bo Yao, Song Liu, Yaoqi Zhou, Chi Zhang

School of Biological Sciences: Faculty Publications

Transcription factors (TFs) play important roles in plants. However, there is no systematic study of their structures and functions of most TFs in plants. Here, we performed template-based structure prediction for all TFs in Arabidopsis thaliana, with their full-length sequences as well as C-terminal and N-terminal regions. A total of 2,918 model structures were obtained with a high confidence score. We find that TF families employ only a smaller number of templates for DNA-binding domains (DBD) but a diverse number of templates for transcription regulatory domains (TRD). Although TF families are classified according to DBD, their sizes have a significant …

Evolution Of A Large, Conserved, And Syntenic Gene Family In Insects, Neethu Shah, Douglas R. Dorer, Etsuko N. Moriyama, Alan C. Christensen

School of Biological Sciences: Faculty Publications

The Osiris gene family, first described in Drosophila melanogaster, is clustered in the genomes of all Drosophila species sequenced to date. In D. melanogaster, it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one of the largest syntenic blocks in the Drosophila group. By examining the genome sequences of other insects in a wide range of taxonomic orders, we show here that the gene family is well-conserved and syntenic not only in the diptera but across the holometabolous and hemimetabolous insects. …

Survival Of The Fittest: Overcoming Oxidative Stress At The Extremes Of Acid, Heat And Metal, Yukari Maezato, Paul H. Blum

School of Biological Sciences: Faculty Publications

The habitat of metal respiring acidothermophilic lithoautotrophs is perhaps the most oxidizing environment yet identified. Geothermal heat, sulfuric acid and transition metals contribute both individually and synergistically under aerobic conditions to create this niche. Sulfuric acid and metals originating from sulfidic ores catalyze oxidative reactions attacking microbial cell surfaces including lipids, proteins and glycosyl groups. Sulfuric acid ����� ��������� ������������ ������������ ������������� ��� ���� ���������� ��� ������ �������� carbon. Oxidative reactions leading to abstraction of electrons is further impacted by heat through an increase in the proportion of reactant molecules with sufficient energy to react. Collectively these factors and particularly …

Metal Resistance And Lithoautotrophy In The Extreme Thermoacidophile Metallosphaera Sedula, Yukari Maezato, Tyler Johnson, Samuel Mccarthy, Karl Dana, Paul H. Blum

School of Biological Sciences: Faculty Publications

Archaea such as Metallosphaera sedula are thermophilic lithoautotrophs that occupy unusually acidic and metal-rich environments. These traits are thought to underlie their industrial importance for bioleaching of base and precious metals. In this study, a genetic approach was taken to investigate the specific relationship between metal resistance and lithoautotrophy during biotransformation of the primary copper ore, chalcopyrite (CuFeS₂). In this study, a genetic system was developed for M. sedula to investigate parameters that limit bioleaching of chalcopyrite. The functional role of the M. sedula copRTA operon was demonstrated by cross-species complementation of a copper-sensitive Sulfolobus solfataricus copR mutant. …