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Glutaredoxins and iron-sulfur protein biogenesis at the interface of redox biology and iron metabolism.
Mühlenhoff, U, Braymer, JJ, Christ, S, Rietzschel, N, Uzarska, MA, Weiler, BD, Lill, R
Biological chemistry. 2020;(12):1407-1428
Abstract
The physiological roles of the intracellular iron and redox regulatory systems are intimately linked. Iron is an essential trace element for most organisms, yet elevated cellular iron levels are a potent generator and amplifier of reactive oxygen species and redox stress. Proteins binding iron or iron-sulfur (Fe/S) clusters, are particularly sensitive to oxidative damage and require protection from the cellular oxidative stress protection systems. In addition, key components of these systems, most prominently glutathione and monothiol glutaredoxins are involved in the biogenesis of cellular Fe/S proteins. In this review, we address the biochemical role of glutathione and glutaredoxins in cellular Fe/S protein assembly in eukaryotic cells. We also summarize the recent developments in the role of cytosolic glutaredoxins in iron metabolism, in particular the regulation of fungal iron homeostasis. Finally, we discuss recent insights into the interplay of the cellular thiol redox balance and oxygen with that of Fe/S protein biogenesis in eukaryotes.
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Zinc homeostasis in the secretory pathway in yeast.
Bird, AJ, Wilson, S
Current opinion in chemical biology. 2020;:145-150
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Abstract
It is estimated that up to 10% of proteins in eukaryotes require zinc for their function. Although the majority of these proteins are located in the nucleus and cytosol, a small subset is secreted from cells or is located within an intracellular compartment. As many of these compartmentalized metalloproteins fold to their native state and bind their zinc cofactor inside an organelle, cells require mechanisms to maintain supply of zinc to these compartments even under conditions of zinc deficiency. At the same time, intracellular compartments can also be the site for storing zinc ions, which then can be mobilized when needed. In this review, we highlight insight that has been obtained from yeast models about how zinc homeostasis is maintained in the secretory pathway and vacuole.
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Aspects of Multicellularity in Saccharomyces cerevisiae Yeast: A Review of Evolutionary and Physiological Mechanisms.
Opalek, M, Wloch-Salamon, D
Genes. 2020;(6)
Abstract
The evolutionary transition from single-celled to multicellular growth is a classic and intriguing problem in biology. Saccharomyces cerevisiae is a useful model to study questions regarding cell aggregation, heterogeneity and cooperation. In this review, we discuss scenarios of group formation and how this promotes facultative multicellularity in S. cerevisiae. We first describe proximate mechanisms leading to aggregation. These mechanisms include staying together and coming together, and can lead to group heterogeneity. Heterogeneity is promoted by nutrient limitation, structured environments and aging. We then characterize the evolutionary benefits and costs of facultative multicellularity in yeast. We summarize current knowledge and focus on the newest state-of-the-art discoveries that will fuel future research programmes aiming to understand facultative microbial multicellularity.
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Induction of protein aggregation and starvation response by tRNA modification defects.
Klassen, R, Bruch, A, Schaffrath, R
Current genetics. 2020;(6):1053-1057
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Abstract
Posttranscriptional modifications of anticodon loops contribute to the decoding efficiency of tRNAs by supporting codon recognition and loop stability. Consistently, strong synthetic growth defects are observed in yeast strains simultaneously lacking distinct anticodon loop modifications. These phenotypes are accompanied by translational inefficiency of certain mRNAs and disturbed protein homeostasis resulting in accumulation of protein aggregates. Different combinations of anticodon loop modification defects were shown to affect distinct tRNAs but provoke common transcriptional changes that are reminiscent of the cellular response to nutrient starvation. Multiple mechanisms may be involved in mediating inadequate starvation response upon loss of critical tRNA modifications. Recent evidence suggests protein aggregate induction to represent one such trigger.
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Regulation of nutrient transporters by metabolic and environmental stresses.
Babst, M
Current opinion in cell biology. 2020;:35-41
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Abstract
The yeast plasma membrane is a selective barrier between an erratic environment and the cell's metabolism. Nutrient transporters are the gatekeepers that control the import of molecules feeding into the metabolic pathways. Nutrient import adjusts rapidly to changes in metabolism and the environment, which is accomplished by regulating the surface expression of transporters. Recent studies indicate that the lipid environment in which transporters function regulates ubiquitination efficiency and endocytosis of these proteins. Changes in the lipid environment are caused by lateral movements of the transporters between different membrane domains and by the influence of the extracellular environment on the fluidity of the plasma membrane.
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Engineering Critical Enzymes and Pathways for Improved Triterpenoid Biosynthesis in Yeast.
Guo, H, Wang, H, Huo, YX
ACS synthetic biology. 2020;(9):2214-2227
Abstract
Triterpenoids represent a diverse group of phytochemicals that are widely distributed in the plant kingdom and have many biological activities. The heterologous production of triterpenoids in Saccharomyces cerevisiae has been successfully implemented by introducing various triterpenoid biosynthetic pathways. By engineering related enzymes as well as through yeast metabolism, the yield of various triterpenoids is significantly improved from the milligram per liter scale to the gram per liter scale. This achievement demonstrates that engineering critical enzymes is considered a potential strategy to overcome the main hurdles of the industrial application of these potent natural products. Here, we review strategies for designing enzymes to improve the yield of triterpenoids in S. cerevisiae in terms of three main aspects: 1, elevating the supply of the precursor 2,3-oxidosqualene; 2, optimizing triterpenoid-involved reactions; and 3, lowering the competition of the native sterol pathway. Then, we provide challenges and prospects for further enhancing triterpenoid production in S. cerevisiae.
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Lager-brewing yeasts in the era of modern genetics.
Gorter de Vries, AR, Pronk, JT, Daran, JG
FEMS yeast research. 2019;(7)
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Abstract
The yeast Saccharomyces pastorianus is responsible for the annual worldwide production of almost 200 billion liters of lager-type beer. S. pastorianus is a hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus that has been studied for well over a century. Scientific interest in S. pastorianus intensified upon the discovery, in 2011, of its S. eubayanus ancestor. Moreover, advances in whole-genome sequencing and genome editing now enable deeper exploration of the complex hybrid and aneuploid genome architectures of S. pastorianus strains. These developments not only provide novel insights into the emergence and domestication of S. pastorianus but also generate new opportunities for its industrial application. This review paper combines historical, technical and socioeconomic perspectives to analyze the evolutionary origin and genetics of S. pastorianus. In addition, it provides an overview of available methods for industrial strain improvement and an outlook on future industrial application of lager-brewing yeasts. Particular attention is given to the ongoing debate on whether current S. pastorianus originates from a single or multiple hybridization events and to the potential role of genome editing in developing industrial brewing yeast strains.
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New insights on yeast and filamentous fungus adhesion in a natural co-immobilization system: proposed advances and applications in wine industry.
Ogawa, M, Bisson, LF, García-Martínez, T, Mauricio, JC, Moreno-García, J
Applied microbiology and biotechnology. 2019;(12):4723-4731
Abstract
Fungi possess extraordinary strength in attachment to biotic and abiotic surfaces. This review focuses on adhesion mechanisms of yeast and filamentous fungi and the proposed combination of the adhesive forces of both organisms in an immobilization system called yeast biocapsules, whereby Saccharomyces cerevisiae cells are attached to the hyphae of Penicillium chrysogenum. The natural adherent properties of each organism, one multicellular and another unicellular, allow yeast to be fixated securely on the filamentous fungi and complete alcoholic fermentation. Following alcoholic fermentation, the hyphae become an inert support for yeast cells while maintaining shape and integrity. Biocapsules have been used successfully in both wine and bioethanol production. Investigation of the potential genes involved in fungal-yeast fusion suggests that natural hydrophobic interactions of both organisms play a major role. Analysis of the possible mechanisms involved in fungus and yeast adhesion, future perspectives on improving yeast immobilization, and proposed applications of the biocapsules are explored.
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The problem of genetic code misreading during protein synthesis.
Joshi, K, Cao, L, Farabaugh, PJ
Yeast (Chichester, England). 2019;(1):35-42
Abstract
Saccharomyces cerevisiae has been an important model for determining the frequency of translational misreading events, those in which a tRNA pairs incorrectly to the mRNA and inserts an amino acid not specified by the codon in the mRNA. Misreading errors have been quantified in vivo using reporter protein systems or mass spectrometry with both approaches converging on a simple model for most misreading. The available data show that misreading tRNAs must form stereotypical base mismatches that correspond to those that can mimic Watson-Crick base pairs when formed in the ribosomal A site. Errors involving other mismatches occur significantly less frequently. This work debunks the idea of an average misreading frequency of 5 × 10-4 per codon that extends across the genetic code. Instead, errors come in two distinct classes-high frequency and low frequency events-with most errors being of the low frequency type. A comparison of misreading errors in S. cerevisiae and Escherichia coli suggests the existence of a mechanism that reduces misreading frequency in yeast; this mechanism may operate in eukaryotes generally.
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Cross-talk in NAD+ metabolism: insights from Saccharomyces cerevisiae.
James Theoga Raj, C, Lin, SJ
Current genetics. 2019;(5):1113-1119
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Abstract
NAD+ (nicotinamide adenine dinucleotide) is an essential metabolite involved in a myriad of cellular processes. The NAD+ pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human with some species-specific differences. Studying the regulation of NAD+ metabolism has been difficult due to the dynamic flexibility of NAD+ intermediates, the redundancy of biosynthesis pathways, and the complex interconnections among them. The budding yeast Saccharomyces cerevisiae provides an efficient genetic model for the isolation and study of factors that regulate specific NAD+ biosynthesis pathways. A recent study has uncovered a putative cross-regulation between the de novo NAD+ biosynthesis and copper homeostasis mediated by a copper-sensing transcription factor Mac1. Mac1 appears to work with the Hst1-Sum1-Rfm1 complex to repress the expression of de novo NAD+ biosynthesis genes. Here, we extend the discussions to include additional nutrient- and stress-sensing pathways that have been associated with the regulation of NAD+ homeostasis. NAD+ metabolism is an emerging therapeutic target for several human diseases. NAD+ preservation also helps ameliorate age-associated metabolic disorders. Recent findings in yeast contribute to the understanding of the molecular basis underlying the cross-regulation of NAD+ metabolism and other signaling pathways.