Proline Biosynthesis Is Required for Endoplasmic Reticulum Stress Tolerance in Saccharomyces cerevisiae

Dickman, Martin B.; Becker, Donald F.

doi:10.1074/jbc.m114.562827

Cited by 39 publications

(27 citation statements)

References 80 publications

(91 reference statements)

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“…2D). This reflects the specificities of the metabolic network of proline, which cannot be further catabolized by yeast under anaerobiosis (31) (Fig. 3A): proline is synthesized directly from intracellular glutamate (32), and equimolar production of proline results from the catabolism of arginine (17).…”

Section: Resultsmentioning

confidence: 99%

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Crépin

Truong

Bloem

et al. 2017

Appl Environ Microbiol

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During fermentative growth in natural and industrial environments, Saccharomyces cerevisiae must redistribute the available nitrogen from multiple exogenous sources to amino acids in order to suitably fulfill anabolic requirements. To exhaustively explore the management of this complex resource, we developed an advanced strategy based on the reconciliation of data from a set of stable isotope tracer experiments with labeled nitrogen sources. Thus, quantifying the partitioning of the N compounds through the metabolism network during fermentation, we demonstrated that, contrary to the generally accepted view, only a limited fraction of most of the consumed amino acids is directly incorporated into proteins. Moreover, substantial catabolism of these molecules allows for efficient redistribution of nitrogen, supporting the operative de novo synthesis of proteinogenic amino acids. In contrast, catabolism of consumed amino acids plays a minor role in the formation of volatile compounds. Another important feature is that the ␣-keto acid precursors required for the de novo syntheses originate mainly from the catabolism of sugars, with a limited contribution from the anabolism of consumed amino acids. This work provides a comprehensive view of the intracellular fate of consumed nitrogen sources and the metabolic origin of proteinogenic amino acids, highlighting a strategy of distribution of metabolic fluxes implemented by yeast as a means of adapting to environments with changing and scarce nitrogen resources. IMPORTANCE A current challenge for the wine industry, in view of the extensive competition in the worldwide market, is to meet consumer expectations regarding the sensory profile of the product while ensuring an efficient fermentation process. Understanding the intracellular fate of the nitrogen sources available in grape juice is essential to the achievement of these objectives, since nitrogen utilization affects both the fermentative activity of yeasts and the formation of flavor compounds. However, little is known about how the metabolism operates when nitrogen is provided as a composite mixture, as in grape must. Here we quantitatively describe the distribution through the yeast metabolic network of the N moieties and C backbones of these nitrogen sources. Knowledge about the management of a complex resource, which is devoted to improvement of the use of the scarce N nutrient for growth, will be useful for better control of the fermentation process and the sensory quality of wines.KEYWORDS complex nitrogen resource, metabolic network, metabolism, nitrogen, quantitative analysis, regulation, yeasts T he management of nutrients provided by the external environment, mainly carbon and nitrogen, and their redistribution inside the cells for the formation of biosynthetic precursors through the metabolic network are essential for all living organisms. The topology of the metabolic network of the yeast Saccharomyces cerevisiae is one of

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Section: Resultsmentioning

confidence: 99%

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Crépin

Truong

Bloem

et al. 2017

Appl Environ Microbiol

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“…Proline is a multifaceted amino acid with important roles in carbon and nitrogen metabolism; protein synthesis; and protection against various environmental factors such as drought (44), metal toxicity (45,46), osmotic stress (24,25), ultraviolent irradiation (47), unfolded protein stress (26,48), and oxidative stress (19,23,27,28,49). In this study, we explored the role of proline metabolism in oxidative stress protection by characterizing the oxidative stress response of wild-type and putA mutant E. coli strains.…”

Section: Discussionmentioning

confidence: 99%

Proline Metabolism IncreaseskatGExpression and Oxidative Stress Resistance in Escherichia coli

2014

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The oxidation of L-proline to glutamate in Gram-negative bacteria is catalyzed by the proline utilization A (PutA) flavoenzyme, which contains proline dehydrogenase (PRODH) and ⌬ 1 -pyrroline-5-carboxylate (P5C) dehydrogenase domains in a single polypeptide. Previous studies have suggested that aside from providing energy, proline metabolism influences oxidative stress resistance in different organisms. To explore this potential role and the mechanism, we characterized the oxidative stress resistance of wild-type and putA mutant strains of Escherichia coli. Initial stress assays revealed that the putA mutant strain was significantly more sensitive to oxidative stress than the parental wild-type strain. Expression of PutA in the putA mutant strain restored oxidative stress resistance, confirming that depletion of PutA was responsible for the oxidative stress phenotype. Treatment of wild-type cells with proline significantly increased hydroperoxidase I (encoded by katG) expression and activity. Furthermore, the ⌬katG strain failed to respond to proline, indicating a critical role for hydroperoxidase I in the mechanism of proline protection. The global regulator OxyR activates the expression of katG along with several other genes involved in oxidative stress defense. In addition to katG, proline increased the expression of grxA (glutaredoxin 1) and trxC (thioredoxin 2) of the OxyR regulon, implicating OxyR in proline protection. Proline oxidative metabolism was shown to generate hydrogen peroxide, indicating that proline increases oxidative stress tolerance in E. coli via a preadaptive effect involving endogenous hydrogen peroxide production and enhanced catalase-peroxidase activity.T he conversion of L-proline to glutamate is a four-electron oxidation process that is coordinated in two successive steps by the enzymes proline dehydrogenase (PRODH) and ⌬ 1 -pyrroline-5-carboxylate dehydrogenase (P5CDH) (Fig. 1) (1). In eukaryotes, PRODH and P5CDH are separately encoded enzymes localized in the mitochondrion. In Gram-negative bacteria, PRODH and P5CDH are combined into a bifunctional enzyme known as proline utilization A (PutA) (1, 2). The PRODH domain contains a noncovalently bound flavin adenine dinucleotide (FAD) cofactor and couples the two-electron oxidation of proline to the reduction of ubiquinone in the cytoplasmic membrane (3). The product of the PRODH reaction, ⌬ 1 -pyrroline-5-carboxylate (P5C), is subsequently hydrolyzed to glutamate-␥-semialdehyde (GSA), which is then oxidized to glutamate by the NAD ϩ -dependent P5CDH domain (2). In certain Gram-negative bacteria such as Escherichia coli, PutA also has an N-terminal ribbon-helix-helix (RHH) DNA-binding domain (residues 1 to 47) (4). The RHH domain enables PutA to act as an autogenous transcriptional regulator of the putA and putP (highaffinity Na ϩ -proline transporter) genes (4). PutA represses put gene expression by binding to five operator sites in the put regulatory region (5). Transcription of the put genes is activated by proline, which causes a r...

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“…Besides its proteogenic function, proline has roles in energy utilization ( Hare and Cress, 1997 ), reactive oxygen species (ROS) generation ( Donald et al, 2001 ; Szekely et al, 2008 ; Liu et al, 2012b ), programmed cell death (PCD; Donald et al, 2001 ; Liu et al, 2012b ), unfolded protein response ( Liang et al, 2014 ), cell reprogramming and development ( Pistollato et al, 2010 ; Funck et al, 2012 ; D’Aniello et al, 2015 ), stress resistance ( Strizhov et al, 1997 ; Krishnan et al, 2008 ; Szekely et al, 2008 ; Szabados and Savoure, 2010 ), and aging ( Zarse et al, 2012 ; Pang and Curran, 2014 ). In plants, proline metabolism has been proposed to provide stress protection by helping maintain NADPH/NADP + balance, GSH levels, and during pathogen infection, drive the oxidative burst of the hypersensitive response (HR; Miller et al, 2009 ; Ben Rejeb et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Connecting proline metabolism and signaling pathways in plant senescence

2015

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The amino acid proline has a unique biological role in stress adaptation. Proline metabolism is manipulated under stress by multiple and complex regulatory pathways and can profoundly influence cell death and survival in microorganisms, plants, and animals. Though the effects of proline are mediated by diverse signaling pathways, a common theme appears to be the generation of reactive oxygen species (ROS) due to proline oxidation being coupled to the respiratory electron transport chain. Considerable research has been devoted to understand how plants exploit proline metabolism in response to abiotic and biotic stress. Here, we review potential mechanisms by which proline metabolism influences plant senescence, namely in the petal and leaf. Recent studies of petal senescence suggest proline content is manipulated to meet energy demands of senescing cells. In the flower and leaf, proline metabolism may influence ROS signaling pathways that delay senescence progression. Future studies focusing on the mechanisms by which proline metabolic shifts occur during senescence may lead to novel methods to rescue crops under stress and to preserve post-harvest agricultural products.

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Proline Biosynthesis Is Required for Endoplasmic Reticulum Stress Tolerance in Saccharomyces cerevisiae

Cited by 39 publications

References 80 publications

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Proline Metabolism IncreaseskatGExpression and Oxidative Stress Resistance in Escherichia coli

Connecting proline metabolism and signaling pathways in plant senescence

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