scholarly journals Maltotriose consumption by hybrid Saccharomyces pastorianus is heterotic and results from regulatory cross-talk between parental sub-genomes

2019 ◽  
Author(s):  
Nick Brouwers ◽  
Anja Brickwedde ◽  
Arthur R. Gorter de Vries ◽  
Marcel van den Broek ◽  
Susan M. Weening ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Cross Talk ◽  
Molecular Mechanisms ◽  
Alcoholic Beverage ◽  
Evolutionary Origin ◽  
Transcription Activator ◽  
High Sequence Identity ◽  
Maltose Metabolism ◽  
Saccharomyces Pastorianus ◽  
Lager Beer

AbstractS. pastorianus strains are hybrids of S. cerevisiae and S. eubayanus that have been domesticated for several centuries in lager-beer brewing environments. As sequences and structures of S. pastorianus genomes are being resolved, molecular mechanisms and evolutionary origin of several industrially relevant phenotypes remain unknown. This study investigates how maltotriose metabolism, a key feature in brewing, may have arisen in early S. eubayanus × S. cerevisiae hybrids. To address this question, we generated a near-complete genome assembly of Himalayan S. eubayanus strains of the Holarctic subclade. This group of strains have been proposed to be the origin of the S. eubayanus subgenome of current S. pastorianus strains. The Himalayan S. eubayanus genomes harbored several copies of a SeAGT1 α-oligoglucoside transporter gene with high sequence identity to genes encountered in S. pastorianus. Although Himalayan S. eubayanus strains are unable to grown on maltose and maltotriose, their maltose-hydrolase and SeMALT1 and SeAGT1 maltose-transporter genes complemented the corresponding null mutants of S. cerevisiae. Expression, in a Himalayan S. eubayanus strain, of a functional S. cerevisiae maltose-metabolism regulator gene (MALx3) enabled growth on oligoglucosides. The hypothesis that the maltotriose-positive phenotype in S. pastorianus is a result of heterosis was experimentally tested by constructing a S. cerevisiae × S. eubayanus laboratory hybrid with a complement of maltose-metabolism genes that resembles that of current S. pastorianus strains. The ability of this hybrid to consume maltotriose in brewer’s wort demonstrated regulatory cross talk between sub-genomes and thereby validated this hypothesis. These results provide experimental evidence of the evolutionary origin of an essential phenotype of lager-brewing strains and valuable knowledge for industrial exploitation of laboratory-made S. pastorianus-like hybrids.ImportanceS.pastorianus, a S.cerevisiae X S.eubayanus hybrid, is used for production of lager beer, the most produced alcoholic beverage worldwide It emerged by spontaneous hybridization and have colonized early lager-brewing processes. Despite accumulation and analysis of genome sequencing data of S.pastorianus parental genomes, the genetic blueprint of industrially relevant phenotypes remains unknown. Assimilation of wort abundant sugar maltotriose has been postulated to be inherited from S.cerevisiae parent. Here, we demonstrate that although Asian S.eubayanus isolates harbor a functional maltotriose transporter SeAGT1 gene, they are unable to grow on α-oligoglucosides, but expression of S. cerevisae regulator ScMAL13 was sufficient to restore growth on trisaccharides. We hypothesized that S. pastorianus maltotriose phenotype results from regulatory interaction between S.cerevisae maltose transcription activator and the promoter of SeAGT1. We experimentally confirmed the heterotic nature of the phenotype and thus this results provide experimental evidence of the evolutionary origin of an essential phenotype of lager-brewing strains.

scholarly journals Himalayan Saccharomyces eubayanus Genome Sequences Reveal Genetic Markers Explaining Heterotic Maltotriose Consumption by Saccharomyces pastorianus Hybrids

2019 ◽  
Vol 85 (22) ◽  
Author(s):  
Nick Brouwers ◽  
Anja Brickwedde ◽  
Arthur R. Gorter de Vries ◽  
Marcel van den Broek ◽  
Susan M. Weening ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Alcoholic Beverage ◽  
Evolutionary Origin ◽  
Transcription Activator ◽  
High Sequence Identity ◽  
Content Type ◽  
Maltose Metabolism ◽  
Saccharomyces Pastorianus ◽  
Lager Beer ◽  
Saccharomyces Eubayanus

ABSTRACT Saccharomyces pastorianus strains are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus that have been domesticated for centuries in lager beer brewing environments. As sequences and structures of S. pastorianus genomes are being resolved, molecular mechanisms and evolutionary origins of several industrially relevant phenotypes remain unknown. This study investigates how maltotriose metabolism, a key feature in brewing, may have arisen in early S. eubayanus × S. cerevisiae hybrids. To address this question, we generated a nearly complete genome assembly of Himalayan S. eubayanus strains of the Holarctic subclade. This group of strains has been proposed to be the S. eubayanus subgenome origin of current S. pastorianus strains. The Himalayan S. eubayanus genomes harbored several copies of an S. eubayanus AGT1 (SeAGT1) α-oligoglucoside transporter gene with high sequence identity to genes encountered in S. pastorianus. Although Himalayan S. eubayanus strains cannot grow on maltose and maltotriose, their maltose-hydrolase and SeMALT1 and SeAGT1 maltose transporter genes complemented the corresponding null mutants of S. cerevisiae. Expression, in Himalayan S. eubayanus of a functional S. cerevisiae maltose metabolism regulator gene (MALx3) enabled growth on oligoglucosides. The hypothesis that the maltotriose-positive phenotype in S. pastorianus is a result of heterosis was experimentally tested by constructing an S. cerevisiae × S. eubayanus laboratory hybrid with a complement of maltose metabolism genes that resembles that of current S. pastorianus strains. The ability of this hybrid to consume maltotriose in brewer’s wort demonstrated regulatory cross talk between subgenomes and thereby validated this hypothesis. These results support experimentally the new postulated hypothesis on the evolutionary origin of an essential phenotype of lager brewing strains and valuable knowledge for industrial exploitation of laboratory-made S. pastorianus-like hybrids. IMPORTANCE S. pastorianus, an S. cerevisiae × S. eubayanus hybrid, is used for production of lager beer, the most produced alcoholic beverage worldwide. It emerged by spontaneous hybridization and colonized early lager brewing processes. Despite accumulation and analysis of genome sequencing data of S. pastorianus parental genomes, the genetic blueprint of industrially relevant phenotypes remains unresolved. Assimilation of maltotriose, an abundant sugar in wort, has been postulated to be inherited from the S. cerevisiae parent. Here, we demonstrate that although Asian S. eubayanus isolates harbor a functional maltotriose transporter SeAGT1 gene, they are unable to grow on α-oligoglucosides, but expression of S. cerevisiae regulator MAL13 (ScMAL13) was sufficient to restore growth on trisaccharides. We hypothesized that the S. pastorianus maltotriose phenotype results from regulatory interaction between S. cerevisiae maltose transcription activator and the promoter of SeAGT1. We experimentally confirmed the heterotic nature of the phenotype, and thus these results provide experimental evidence of the evolutionary origin of an essential phenotype of lager brewing strains.

scholarly journals A Large Set of Newly Created Interspecific Saccharomyces Hybrids Increases Aromatic Diversity in Lager Beers

2015 ◽  
Vol 81 (23) ◽  
pp. 8202-8214 ◽  
Author(s):  
Stijn Mertens ◽  
Jan Steensels ◽  
Veerle Saels ◽  
Gert De Rouck ◽  
Guido Aerts ◽  
...  
Keyword(s):  
Large Scale ◽  
Alcoholic Beverage ◽  
Pilot Scale ◽  
Temperature Tolerance ◽  
Large Set ◽  
Lager Yeast ◽  
Content Type ◽  
High Attenuation ◽  
Saccharomyces Pastorianus ◽  
Lager Beer

ABSTRACTLager beer is the most consumed alcoholic beverage in the world. Its production process is marked by a fermentation conducted at low (8 to 15°C) temperatures and by the use ofSaccharomyces pastorianus, an interspecific hybrid betweenSaccharomyces cerevisiaeand the cold-tolerantSaccharomyces eubayanus. Recent whole-genome-sequencing efforts revealed that the currently available lager yeasts belong to one of only two archetypes, “Saaz” and “Frohberg.” This limited genetic variation likely reflects that all lager yeasts descend from only two separate interspecific hybridization events, which may also explain the relatively limited aromatic diversity between the available lager beer yeasts compared to, for example, wine and ale beer yeasts. In this study, 31 novel interspecific yeast hybrids were developed, resulting from large-scale robot-assisted selection and breeding between carefully selected strains ofS. cerevisiae(six strains) andS. eubayanus(two strains). Interestingly, many of the resulting hybrids showed a broader temperature tolerance than their parental strains and referenceS. pastorianusyeasts. Moreover, they combined a high fermentation capacity with a desirable aroma profile in laboratory-scale lager beer fermentations, thereby successfully enriching the currently available lager yeast biodiversity. Pilot-scale trials further confirmed the industrial potential of these hybrids and identified one strain, hybrid H29, which combines a fast fermentation, high attenuation, and the production of a complex, desirable fruity aroma.

scholarly journals Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

2014 ◽  
Vol 25 (22) ◽  
pp. 3654-3671 ◽  
Author(s):  
Changsheng Lin ◽  
Jason Ear ◽  
Krishna Midde ◽  
Inmaculada Lopez-Sanchez ◽  
Nicolas Aznar ◽  
...  
Keyword(s):  
Growth Factor ◽  
G Proteins ◽  
Protein Interaction ◽  
Cross Talk ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Growth Factor Receptors ◽  
Structural Basis ◽  
Nucleotide Exchange ◽  
Protein Protein Interaction

A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs.

scholarly journals Molecular mechanisms of BMP-induced bone formation: Cross-talk between BMP and NF-κB signaling pathways in osteoblastogenesis

2010 ◽  
Vol 46 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Eijiro Jimi ◽  
Shizu Hirata ◽  
Masashi Shin ◽  
Masato Yamazaki ◽  
Hidefumi Fukushima
Keyword(s):  
Bone Formation ◽  
Signaling Pathways ◽  
Cross Talk ◽  
Molecular Mechanisms

scholarly journals Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication

IUCrJ ◽  
2018 ◽  
Vol 5 (6) ◽  
pp. 866-879 ◽  
Author(s):  
Woo-Chang Chung ◽  
Junsoo Kim ◽  
Byung Chul Kim ◽  
Hye-Ri Kang ◽  
JongHyeon Son ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Lytic Replication ◽  
Transcription Activator ◽  
Interacting Protein ◽  
Murine Gammaherpesvirus ◽  
Unit Structure ◽  
Parp 1

Poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme that modifies nuclear proteins by poly(ADP-ribosyl)ation, regulates various cellular activities and restricts the lytic replication of oncogenic gammaherpesviruses by inhibiting the function of replication and transcription activator (RTA), a key switch molecule of the viral life cycle. A viral PARP-1-interacting protein (vPIP) encoded by murine gammaherpesvirus 68 (MHV-68) orf49 facilitates lytic replication by disrupting interactions between PARP-1 and RTA. Here, the structure of MHV-68 vPIP was determined at 2.2 Å resolution. The structure consists of 12 α-helices with characteristic N-terminal β-strands (Nβ) and forms a V-shaped-twist dimer in the asymmetric unit. Structure-based mutagenesis revealed that Nβ and the α1 helix (residues 2–26) are essential for the nuclear localization and function of vPIP; three residues were then identified (Phe5, Ser12 and Thr16) that were critical for the function of vPIP and its interaction with PARP-1. A recombinant MHV-68 harboring mutations of these three residues showed severely attenuated viral replication both in vitro and in vivo. Moreover, ORF49 of Kaposi's sarcoma-associated herpesvirus also directly interacted with PARP-1, indicating a conserved mechanism of action of vPIPs. The results elucidate the novel molecular mechanisms by which oncogenic gammaherpesviruses overcome repression by PARP-1 using vPIPs.

scholarly journals Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Zhu ◽  
Ming Qiao ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Liver Fibrosis ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Docking Simulation ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Transcription Activator ◽  
Active Ingredients ◽  
Oxidoreductase Activity

Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

P-Selectin-β2-Integrin Cross-Talk: A Molecular Mechanism For Polymorphonuclear Leukocyte Recruitment At The Site Of Vascular Damage

1999 ◽  
Vol 82 (08) ◽  
pp. 787-793 ◽  
Author(s):  
Virgilio Evangelista ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Cross Talk ◽  
Molecular Mechanisms ◽  
Vascular Damage ◽  
Tissue Integrity ◽  
Β2 Integrin ◽  
Leukocyte Accumulation ◽  
Platelet Thrombus ◽  
And Migration ◽  
The One ◽  
Pmn Leukocyte

IntroductionPlatelets activated at the site of vascular damage play a pivotal role in polymorphonuclear (PMN) leukocyte accumulation in a growing thrombus2,3 and may substitute endothelial cells in the recruitment and migration of leukocytes through damaged vessel wall.4 Leukocytes, accumulated in a platelet thrombus, can contribute to further platelet activation5 and to increased fibrin deposition.6 These events, on the one hand, may contribute to the maintenance of vascular and tissue integrity. They may, however, play a pathogenic role in inflammatory and thrombotic disease, providing some biological plausibility to the epidemiological evidence of significant association between leukocyte count and the incidence of coronary heart disease.7,8 We shall focus our attention on the molecular mechanisms involved in the recruitment of PMN leukocytes on activated platelets as it occurs at the site of vascular damage, with particular attention to P-selectin- β2-integrin cross-talk.

Hemagglutinin protein of measles virus induces apoptosis of HeLa cells via both extrinsic and intrinsic pathways

2013 ◽  
Vol 59 (12) ◽  
pp. 814-824 ◽  
Author(s):  
Changhua Yi ◽  
Xin Liu ◽  
Yingle Liu ◽  
Songya Lu ◽  
Yipeng Qi
Keyword(s):  
Cross Talk ◽  
Hela Cells ◽  
Measles Virus ◽  
Molecular Mechanisms ◽  
Envelope Glycoproteins ◽  
Cellular Receptor ◽  
Intrinsic Pathway ◽  
Extrinsic Pathway ◽  
Hemagglutinin Protein ◽  
Cellular Apoptosis

In this study, we investigated the potential for different components of the measles virus (MV) to induce apoptosis of HeLa cells and explored the apoptotic molecular mechanisms. After testing the 2 envelope glycoproteins hemagglutinin (H) and fusion (F), we found that MV H alone was sufficient to induce the apoptosis of HeLa cells, whereas MV F did not. MV F also had no influence on MV-H-mediated apoptosis. MV H could induce cellular apoptosis in HeLa cells through its interaction with the cellular receptor CD46 via both the TRAIL-mediated extrinsic pathway and the mitochondria-controlled intrinsic pathway, and that cross talk between these 2 pathways occurred during the process. These findings extend the functions of MV envelope glycoproteins in the pathogenesis of MV infection and suggest that MV H may be a potential therapeutic in the treatment of some cancers.

scholarly journals New insights into the functions of Cox-2 in skin and esophageal malignancies

2020 ◽  
Vol 52 (4) ◽  
pp. 538-547 ◽  
Author(s):  
Hyeongsun Moon ◽  
Andrew C. White ◽  
Alexander D. Borowsky
Keyword(s):  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Tumor Development ◽  
Cancer Type ◽  
Tumor Initiation ◽  
Cells Of Origin ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Necessary And Sufficient

Abstract Understanding the cellular and molecular mechanisms of tumor initiation and progression for each cancer type is central to making improvements in both prevention and therapy. Identifying the cancer cells of origin and the necessary and sufficient mechanisms of transformation and progression provide opportunities for improved specific clinical interventions. In the last few decades, advanced genetic manipulation techniques have facilitated rapid progress in defining the etiologies of cancers and their cells of origin. Recent studies driven by various groups have provided experimental evidence indicating the cellular origins for each type of skin and esophageal cancer and have identified underlying mechanisms that stem/progenitor cells use to initiate tumor development. Specifically, cyclooxygenase-2 (Cox-2) is associated with tumor initiation and progression in many cancer types. Recent studies provide data demonstrating the roles of Cox-2 in skin and esophageal malignancies, especially in squamous cell carcinomas (SCCs) occurring in both sites. Here, we review experimental evidence aiming to define the origins of skin and esophageal cancers and discuss how Cox-2 contributes to tumorigenesis and differentiation.

Sign in / Sign up

Export Citation Format

Share Document