Carlsberg Laboratory

Copenhagen, Denmark

Carlsberg Laboratory

Copenhagen, Denmark

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Gleadow R.M.,Monash University | Moller B.L.,Copenhagen University | Moller B.L.,Carlsberg Laboratory
Annual Review of Plant Biology | Year: 2014

Cyanogenic glycosides (CNglcs) are bioactive plant products derived from amino acids. Structurally, these specialized plant compounds are characterized as α-hydroxynitriles (cyanohydrins) that are stabilized by glucosylation. In recent years, improved tools within analytical chemistry have greatly increased the number of known CNglcs by enabling the discovery of less abundant CNglcs formed by additional hydroxylation, glycosylation, and acylation reactions. Cyanogenesis - the release of toxic hydrogen cyanide from endogenous CNglcs - is an effective defense against generalist herbivores but less effective against fungal pathogens. In the course of evolution, CNglcs have acquired additional roles to improve plant plasticity, i.e., establishment, robustness, and viability in response to environmental challenges. CNglc concentration is usually higher in young plants, when nitrogen is in ready supply, or when growth is constrained by nonoptimal growth conditions. Efforts are under way to engineer CNglcs into some crops as a pest control measure, whereas in other crops efforts are directed toward their removal to improve food safety. Given that many food crops are cyanogenic, it is important to understand the molecular mechanisms regulating cyanogenesis so that the impact of future environmental challenges can be anticipated. Copyright © 2014 by Annual Reviews.


Breton C.,Joseph Fourier University | Fournel-Gigleux S.,University of Lorraine | Palcic M.M.,Carlsberg Laboratory
Current Opinion in Structural Biology | Year: 2012

Cellular glycome assembly requires the coordinated action of a large number of glycosyltransferases that catalyse the transfer of a sugar residue from a donor to specific acceptor molecules. This enzyme family is very ancient, encompassing all three domains of life. There has been considerable recent progress in structural glycobiology with the determination of crystal structures of several important glycosyltransferase members, showing novel folds and variations around a common α/β scaffold. Structural, kinetic and inhibitor data have led to the emergence of various scenarios with respect to their evolutionary history and reaction mechanisms thus highlighting the different solutions that nature has selected to catalyse glycosyl transfer. © 2012 Elsevier Ltd.


Dockter C.,Carlsberg Laboratory | Hansson M.,Lund University
Journal of Experimental Botany | Year: 2015

The Green Revolution combined advancements in breeding and agricultural practice, and provided food security to millions of people. Daily food supply is still a major issue in many parts of the world and is further challenged by future climate change. Fortunately, life science research is currently making huge progress, and the development of future crop plants will be explored. Today, plant breeding typically follows one gene per trait. However, new scientific achievements have revealed that many of these traits depend on different genes and complex interactions of proteins reacting to various external stimuli. These findings open up new possibilities for breeding where variations in several genes can be combined to enhance productivity and quality. In this review we present an overview of genes determining plant architecture in barley, with a special focus on culm length. Many genes are currently known only through their mutant phenotypes, but emerging genomic sequence information will accelerate their identification. More than 1000 different short-culm barley mutants have been isolated and classified in different phenotypic groups according to culm length and additional pleiotropic characters. Some mutants have been connected to deficiencies in biosynthesis and reception of brassinosteroids and gibberellic acids. Still other mutants are unlikely to be connected to these hormones. The genes and corresponding mutations are of potential interest for development of stiff-straw crop plants tolerant to lodging, which occurs in extreme weather conditions with strong winds and heavy precipitation. © The Author 2015.


Meier S.,Technical University of Denmark | Meier S.,Carlsberg Laboratory | Beeren S.R.,Carlsberg Laboratory
Journal of the American Chemical Society | Year: 2014

We describe a simple method for the simultaneous determination of association constants for a guest binding to seven different hosts in a mixture of more than 20 different oligosaccharides. If the binding parameters are known for one component in the mixture, a single NMR titration suffices to determine binding constants for all other detectable and resolvable hosts. With the use of high-resolution 1H-13C HSQC experiments, complexes of amphiphiles with more than 10 different maltooligosaccharides can be resolved. Hereby, the binding capabilities of a set of structurally related hosts can be quantitatively studied to systematically explore noncovalent interactions without the need to isolate each host. © 2014 American Chemical Society.


Palcic M.M.,Carlsberg Laboratory
Current Opinion in Chemical Biology | Year: 2011

Glycosyltransferases are useful synthetic tools for the preparation of natural oligosaccharides, glycoconjugates and their analogues. High expression levels of recombinant enzymes have allowed their use in multi-step reactions, on mg to multi-gram scales. Since glycosyltransferases are tolerant with respect to utilizing modified donors and acceptor substrates they can be used to prepare oligosaccharide analogues and for diversification of natural products. New sources of enzymes are continually discovered as genomes are sequenced and they are annotated in the Carbohydrate Active Enzyme (CAZy) glycosyltransferase database. Glycosyltransferase mutagenesis, domain swapping and metabolic pathway engineering to change reaction specificity and product diversification are increasingly successful due to advances in structure-function studies and high throughput screening methods. © 2010 Elsevier Ltd.


Holland-Nell K.,Leibniz Insitut fur Molekulare Pharmakologie | Meldal M.,Carlsberg Laboratory
Angewandte Chemie - International Edition | Year: 2011

Click into place: Tachyplesin-I (TP-I) analogues in which both disulfide bridges (1) have been replaced with triazoles (2) represent structural mimetics of TP-I that display similar or slightly improved antibacterial activity. Optimized structures were obtained by replacing the cysteine residues in TP-I by azido- and alkyno-functionalized amino acids. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Beeren S.R.,Carlsberg Laboratory | Hindsgaul O.,Carlsberg Laboratory
Angewandte Chemie - International Edition | Year: 2013

Hang on to those branches! Amylopectin, the major polysaccharide of starch, is a predominantly α(1,4)-linked glucan whose properties are defined by its size and the number, distribution, and length of its α(1,6)-linked branches. The amphiphilic probe HPTS-C16H33 binds to terminal helical branches longer than 12 glucose units (green), which allows for a detailed quantitative characterization of polysaccharide branching by 1H NMR spectroscopy. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Walther A.,Carlsberg Laboratory | Wendland J.,Carlsberg Laboratory
Fungal Genetics and Biology | Year: 2012

Ashbya gossypii is a natural overproducer of riboflavin. Overproduction of riboflavin can be induced by environmental stress, e.g. nutritional or oxidative stress. The Yap-protein family has a well-documented role in stress response. Particularly, Yap1 has a major role in directing the oxidative stress responses. The A. gossypii YAP-family consists of only three genes in contrast to its closest relative Eremothecium cymbalariae, which has four YAP-homologs. Gene order at Eremothecium YAP-loci is conserved with the reconstructed yeast ancestor. AgYap1p is unique amongst Yap-homologs as it lacks the cysteine-rich domains (CRDs). AgYAP1 expression is inducible and GFP-AgYap1 localizes to the nucleus. Agyap1 mutants displayed higher sensitivity against oxidative stress - H2O2 and menadione - and are strongly reduced in riboflavin production. High levels of cAMP, which also reduce riboflavin production, show a synergistic effect on this sensitivity. AgYAP1 and a chimera of AgYAP1 (with the DNA-binding domain) and ScYAP1 (with the CRDs) can both complement the Scyap1 oxidative stress sensitivity. This suggests that the DNA-binding sites of ScYap1 are conserved in A. gossypii. Expression of AgRIB4, which contains three putative Yap1-binding sites, assayed via a lacZ-reporter gene was strongly reduced in an Agyap1 mutant suggesting a direct involvement of AgYap1 in riboflavin production. Furthermore, our data show that application of H2O2 stress leads to an increase in riboflavin production in a Yap1-dependent manner. © 2012 Elsevier Inc.


Wendland J.,Carlsberg Laboratory
Eukaryotic Cell | Year: 2014

Alcoholic fermentations have accompanied human civilizations throughout our history. Lager yeasts have a several-centurylong tradition of providing fresh beer with clean taste. The yeast strains used for lager beer fermentation have long been recognized as hybrids between two Saccharomyces species. We summarize the initial findings on this hybrid nature, the genomics/ transcriptomics of lager yeasts, and established targets of strain improvements. Next-generation sequencing has provided fast access to yeast genomes. Its use in population genomics has uncovered many more hybridization events within Saccharomyces species, so that lager yeast hybrids are no longer the exception from the rule. These findings have led us to propose network evolution within Saccharomyces species. This “web of life” recognizes the ability of closely related species to exchange DNA and thus drain from a combined gene pool rather than be limited to a gene pool restricted by speciation. Within the domesticated lager yeasts, two groups, the Saaz and Frohberg groups, can be distinguished based on fermentation characteristics. Recent evidence suggests that these groups share an evolutionary history. We thus propose to refer to the Saaz group as Saccharomyces carlsbergensis and to the Frohberg group as Saccharomyces pastorianus based on their distinct genomes. New insight into the hybrid nature of lager yeast will provide novel directions for future strain improvement. © 2014, American Society for Microbiology. All Rights Reserved.


Botanists have suspected this possibility since 1980, but supporters have lacked proof. Now, Carlsberg Laboratory's Jesper Harholt and University of Copenhagen's Øjvind Moestrup and Peter Ulvskov present genetic and morphological evidence that corroborates the theory. Notably, traits that land plants use to survive on land today are well conserved in some species of green algae. The collaboration began while Harholt and Ulvskov were studying the evolution of the plant cell wall, long considered to be a key adaptation for a terrestrial lifestyle, as it provides body support for plants growing under the influence of gravity. "We realized that algae have a cell wall that's similarly complex to terrestrial plant cell walls, which seemed peculiar because ancient algae were supposedly growing in water," says Harholt, Science Manager at the Carlsberg Laboratory. "We then started looking for other traits that would support the idea that algae were actually on land before they turned into land plants." Working with Moestrup, an expert in algae, they also explored structures (or rather, the loss of structures) that are hard to explain if algae only lived in water. For example, some green algae have lost their flagella, whip-like organelles that help single-celled organisms move around in water. All of the algae that are close relatives to land plants no longer have an eyespot, which they would use to swim toward light. Cell wall traits combined with the recently sequenced genome of terrestrial green algae Klebsormidium, (published in 2014, DOI: 10.1038/ncomms4978), revealed that this green alga shares a number of genes with land plants related to light tolerance and drought tolerance. With the genetic evidence in hand, we know that the traits have arisen linearly, rather than by convergent evolution. If their theory withstands scrutiny, it would begin to upend what's been cited in textbooks for over a century. The idea that plants jumped from water to land is credited to botanist Frederick Orpen Bower, although it is unclear whether that was his intended argument. In his 1908 tome "The Origin of a Land Flora," he simply proposed that the "invention" of alternating life cycles provided early land plants with a platform—the sporophyte—for evolutionary experimentation and thus adaptability. "With all of the genomic and morphological data we have, it is very hard to explain, evolutionarily-wise, how algae lived in water all the way up to land plants," says Ulvskov, also with Copenhagen's Department of Plant and Environmental Sciences. "We have to turn this thinking on the head—we have the evidence now." The researchers' biggest challenge will be to prove that a period of pre-adaptation led to the complex cell walls of land plants (although about 250 new genes were required for the formation of this terrestrial-friendly cell covering, which helps their case). They believe that these terrestrial green algae were advanced enough to survive on sandy surfaces, living on rain as a source of humidity. But with a small fossil record to go on—only spores exist from this period of evolutionary history—they will need to rely heavily on genetics to make their argument. "The strange thing for me is that if these green algae were terrestrial for a long time, how come that so few of these species are still around?" says Moestrup, an evolutionary biologist. "It could be because they were all outcompeted, but maybe one day we will find more green algae of this lineage." "You have to be patient and sometimes pursue your crazy ideas, even when they differ from the dogmatic thinking in the field," Harholt adds. "If you pile up enough evidence, at some point you may realize that you might be correct." More information: Trends in Plant Science, Harholt et al.: "Why Plants Were Terrestrial From The Beginning" dx.doi.org/10.1016/j.tplants.2015.11.010

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