scholarly journals Adaptations in metabolism and protein translation give rise to the Crabtree effect in yeast

2021 ◽  
Vol 118 (51) ◽  
pp. e2112836118
Author(s):  
Carl Malina ◽  
Rosemary Yu ◽  
Johan Björkeroth ◽  
Eduard J. Kerkhoven ◽  
Jens Nielsen
Keyword(s):  
Glucose Utilization ◽  
Protein Translation ◽  
Central Carbon Metabolism ◽  
Crabtree Effect ◽  
Translation Efficiency ◽  
Or Efficiency ◽  
Central Carbon ◽  
Genome Scale ◽  
Insight Into ◽  
Utilization Strategy

Aerobic fermentation, also referred to as the Crabtree effect in yeast, is a well-studied phenomenon that allows many eukaryal cells to attain higher growth rates at high glucose availability. Not all yeasts exhibit the Crabtree effect, and it is not known why Crabtree-negative yeasts can grow at rates comparable to Crabtree-positive yeasts. Here, we quantitatively compared two Crabtree-positive yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and two Crabtree-negative yeasts, Kluyveromyces marxianus and Scheffersomyces stipitis, cultivated under glucose excess conditions. Combining physiological and proteome quantification with genome-scale metabolic modeling, we found that the two groups differ in energy metabolism and translation efficiency. In Crabtree-positive yeasts, the central carbon metabolism flux and proteome allocation favor a glucose utilization strategy minimizing proteome cost as proteins translation parameters, including ribosomal content and/or efficiency, are lower. Crabtree-negative yeasts, however, use a strategy of maximizing ATP yield, accompanied by higher protein translation parameters. Our analyses provide insight into the underlying reasons for the Crabtree effect, demonstrating a coupling to adaptations in both metabolism and protein translation.

scholarly journals A Genome-Scale Metabolic Model Accurately Predicts Fluxes in Central Carbon Metabolism under Stress Conditions

2010 ◽  
Vol 154 (1) ◽  
pp. 311-323 ◽  
Author(s):  
Thomas C.R. Williams ◽  
Mark G. Poolman ◽  
Andrew J.M. Howden ◽  
Markus Schwarzlander ◽  
David A. Fell ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Metabolic Model ◽  
Central Carbon Metabolism ◽  
Stress Conditions ◽  
A Genome ◽  
Central Carbon ◽  
Genome Scale

scholarly journals Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1496 ◽  
Author(s):  
Laetitia Gibart ◽  
Rajeev Khoodeeram ◽  
Gilles Bernot ◽  
Jean-Paul Comet ◽  
Jean-Yves Trosset
Keyword(s):  
Carbon Metabolism ◽  
Formal Model ◽  
Biological Properties ◽  
Central Carbon Metabolism ◽  
Metabolic Phenotype ◽  
Eukaryotic Cells ◽  
Crabtree Effect ◽  
Modeling Framework ◽  
Cell Microenvironment ◽  
Central Carbon

Adaptation of metabolism is a response of many eukaryotic cells to nutrient heterogeneity in the cell microenvironment. One of these adaptations is the shift from respiratory to fermentative metabolism, also called the Warburg/Crabtree effect. It is a response to a very high nutrient increase in the cell microenvironment, even in the presence of oxygen. Understanding whether this metabolic transition can result from basic regulation signals between components of the central carbon metabolism are the the core question of this work. We use an extension of the René Thomas modeling framework for representing the regulations between the main catabolic and anabolic pathways of eukaryotic cells, and formal methods for confronting models with known biological properties in different microenvironments. The formal model of the regulation of eukaryote metabolism defined and validated here reveals the conditions under which this metabolic phenotype switch occurs. It clearly proves that currently known regulating signals within the main components of central carbon metabolism can be sufficient to bring out the Warburg/Crabtree effect. Moreover, this model offers a general perspective of the regulation of the central carbon metabolism that can be used to study other biological questions.

scholarly journals Toward a Genome Scale Sequence Specific Dynamic Model of Cell-Free Protein Synthesis inEscherichia coli

2017 ◽  
Author(s):  
Nicholas Horvath ◽  
Michael Vilkhovoy ◽  
Joseph A. Wayman ◽  
Kara Calhoun ◽  
James Swartz ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Organic Acids ◽  
Carbon Metabolism ◽  
Protein Production ◽  
Central Carbon Metabolism ◽  
Free Protein ◽  
E Coli ◽  
Central Carbon ◽  
Genome Scale ◽  
Cell Free Protein Synthesis

AbstractCell-free protein expression systems have become widely used in systems and synthetic biology. In this study, we developed an ensemble of dynamicE. colicell-free protein synthesis (CFPS) models. Model parameters were estimated from a training dataset for the cell-free production of a protein product, chloramphenicol acetyltransferase (CAT). The dataset consisted of measurements of glucose, organic acids, energy species, amino acids, and CAT. The ensemble accurately predicted these measurements, especially those of the central carbon metabolism. We then used the trained model to evaluate the optimality of protein production. CAT was produced with an energy efficiency of 12%, suggesting that the process could be further optimized. Reaction group knockouts showed that protein productivity and the metabolism as a whole depend most on oxidative phosphorylation and glycolysis and gluco-neogenesis. Amino acid biosynthesis is also important for productivity, while the overflow metabolism and TCA cycle affect the overall system state. In addition, the translation rate is shown to be more important to productivity than the transcription rate. Finally, CAT production was robust to allosteric control, as was most of the network, with the exception of the organic acids in central carbon metabolism. This study is the first to use kinetic modeling to predict dynamic protein production in a cell-freeE. colisystem, and should provide a foundation for genome scale, dynamic modeling of cell-freeE. coliprotein synthesis.

scholarly journals Minor isozymes tailor yeast metabolism to carbon availability

2018 ◽  
Author(s):  
Patrick H. Bradley ◽  
Patrick A. Gibney ◽  
David Botstein ◽  
Olga G. Troyanskaya ◽  
Joshua D. Rabinowitz
Keyword(s):  
Gene Expression ◽  
Pyruvate Kinase ◽  
Protein Function ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
Carbon Availability ◽  
Central Carbon ◽  
Genome Scale ◽  
Aconitase 2

AbstractIsozymes are enzymes that differ in sequence but catalyze the same chemical reactions. Despite their apparent redundancy, isozymes are often retained over evolutionary time for reasons that can be unclear. We find that, in yeast, isozymes are strongly enriched in central carbon metabolism. Using a gene expression compendium, we find that many isozyme pairs show anticorrelated expression during the respirofermentative shift, suggesting roles in adapting to changing carbon availability. Building on this observation, we assign function to two minor central carbon isozymes, aconitase 2 (ACO2) and pyruvate kinase 2 (PYK2).ACO2is expressed during fermentation and proves advantageous when glucose is limiting.PYK2is expressed during respiration and proves advantageous for growth on three-carbon substrates.PYK2’s deletion is rescued by expressing the major pyruvate kinase, but only if that enzyme carries mutations mirroringPYK2’s allosteric regulation. Thus, central carbon isozymes enable more precise tailoring of metabolism to changing nutrient availability.ImportanceGene duplication is one of the main evolutionary drivers of new protein function. However, some gene duplicates have nevertheless persisted long-term without apparent divergence in biochemical function. Further, under standard lab conditions, many isozymes have subtle or no knockout phenotypes. These factors make it hard to assess the unique contributions of individual isozymes to fitness. We therefore developed a method to identify experimental perturbations that could expose such contributions, and applied it to yeast gene expression data, revealing a potential role for a set of yeast isozymes in adapting to changing carbon sources. Our experimental confirmation of distinct roles for two “minor” yeast isozymes, including one with no previously described knockout phenotype, highlight that even apparently redundant paralogs can have important and unique functions, with implications for genome-scale metabolic modeling and systems-level studies of quantitative genetics.

scholarly journals The transcription factor SlHY5 regulates the ripening of tomato fruit at both the transcriptional and translational levels

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Weihao Wang ◽  
Peiwen Wang ◽  
Xiaojing Li ◽  
Yuying Wang ◽  
Shiping Tian ◽  
...  
Keyword(s):  
Fruit Ripening ◽  
Nutritional Quality ◽  
Ribosomal Proteins ◽  
Anthocyanin Biosynthesis ◽  
Tomato Fruit ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Protein Translation ◽  
Transcriptional Level ◽  
Translation Efficiency

AbstractLight plays a critical role in plant growth and development, but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown. Here, we found that ELONGATED HYPOCOTYL 5 (HY5), a master regulator in the light signaling pathway, is required for normal fruit ripening in tomato (Solanum lycopersicum). Loss of function of tomato HY5 (SlHY5) impairs pigment accumulation and ethylene biosynthesis. Transcriptome profiling identified 2948 differentially expressed genes, which included 1424 downregulated and 1524 upregulated genes, in the Slhy5 mutants. In addition, genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation. Surprisingly, the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants, and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins. Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes. These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery. Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.

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