Austrian Center of Industrial Biotechnology

Graz, Austria

Austrian Center of Industrial Biotechnology

Graz, Austria
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Berg G.,Austrian Center of Industrial Biotechnology | Berg G.,University of Graz | Grube M.,University of Graz | Schloter M.,Helmholtz Center Munich | Smalla K.,Julius Kuhn Institute
Frontiers in Microbiology | Year: 2014

Most eukaryotes develop close interactions with microorganisms that are essential for their performance and survival. Thus, eukaryotes and prokaryotes in nature can be considered as meta-organisms or holobionts. Consequently, microorganisms that colonize different plant compartments contain the plant's second genome. In this respect, many studies in the last decades have shown that plant-microbe interactions are not only crucial for better understanding plant growth and health, but also for sustainable crop production in a changing world. This mini-review acting as editorial presents retrospectives and future perspectives for plant microbiome studies as well as information gaps in this emerging research field. In addition, the contribution of this research topic to the solution of various issues is discussed. © 2014 Berg, Grube, Schloter and Smalla.

Vogl T.,University of Graz | Hartner F.S.,Sandoz GmbH | Glieder A.,Austrian Center of Industrial Biotechnology
Current Opinion in Biotechnology | Year: 2013

Biopharmaceuticals are an integral part of modern medicine and pharmacy. Both, the development and the biotechnological production of biopharmaceuticals are highly cost-intensive and require suitable expression systems. In this review we discuss established and emerging tools for reengineering the methylotrophic yeast Pichia pastoris for biopharmaceutical production. Recent advancements of this industrial expression system through synthetic biology include synthetic promoters to avoid methanol induction and to fine-tune protein production. New platform strains and molecular cloning tools as well as in vivo glycoengineering to produce humanized glycoforms have made P. pastoris an important host for biopharmaceutical production. © 2013 Elsevier Ltd.

Spadiut O.,Vienna University of Technology | Capone S.,Vienna University of Technology | Krainer F.,University of Graz | Glieder A.,Austrian Center of Industrial Biotechnology | Herwig C.,Vienna University of Technology
Trends in Biotechnology | Year: 2014

Monoclonal antibodies (mAbs) and antibody fragments represent the most important biopharmaceutical products today. Because full length antibodies are glycosylated, mammalian cells, which allow human-like N-glycosylation, are currently used for their production. However, mammalian cells have several drawbacks when it comes to bioprocessing and scale-up, resulting in long processing times and elevated costs. By contrast, antibody fragments, that are not glycosylated but still exhibit antigen binding properties, can be produced in microbial organisms, which are easy to manipulate and cultivate. In this review, we summarize recent advances in the expression systems, strain engineering, and production processes for the three main microbials used in antibody and antibody fragment production, namely Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli. © 2013 Elsevier Ltd.

Vogl T.,University of Graz | Glieder A.,University of Graz | Glieder A.,Austrian Center of Industrial Biotechnology
New Biotechnology | Year: 2013

The methylotrophic yeast Pichia pastoris is a widely used host for heterologous protein production. Along with favorable properties such as growth to high cell density and high capacities for protein secretion, P. pastoris provides a strong, methanol inducible promoter of the alcohol oxidase 1 (AOX1) gene. The regulation of this promoter has been extensively studied in recent years by characterizing cis-acting sequence elements and trans-acting factors, revealing insights into underlying molecular mechanisms. However, new alternative promoters have also been identified and characterized by means of their transcriptional regulation and feasibility for protein production using P. pastoris. Besides the often applied GAP promoter, these include a variety of constitutive promoters from housekeeping genes (e.g. TEF1, PGK1, TPI1) and inducible promoters from particular biochemical pathways (e.g. PHO89, THI11, AOD). In addition to these promoter sequence/function based studies, transcriptional regulation has also been investigated by characterizing transcription factors (TFs) and their modes of controlling bioprocess relevant traits. TFs involved in such diverse cellular processes such as the unfolded protein response (UPR) (Hac1p), iron uptake (Fep1p) and oxidative stress response (Yap1p) have been studied. Understanding of these natural transcriptional regulatory networks is a helpful basis for synthetic biology and metabolic engineering approaches that enable the design of tailor-made production strains. © 2012 Elsevier B.V.

Weinhandl K.,Austrian Center of Industrial Biotechnology | Winkler M.,Austrian Center of Industrial Biotechnology | Glieder A.,Austrian Center of Industrial Biotechnology | Camattari A.,University of Graz
Microbial Cell Factories | Year: 2014

Budding yeasts are important expression hosts for the production of recombinant proteins.The choice of the right promoter is a crucial point for efficient gene expression, as most regulations take place at the transcriptional level. A wide and constantly increasing range of inducible, derepressed and constitutive promoters have been applied for gene expression in yeasts in the past; their different behaviours were a reflection of the different needs of individual processes.Within this review we summarize the majority of the large available set of carbon source dependent promoters for protein expression in yeasts, either induced or derepressed by the particular carbon source provided. We examined the most common derepressed promoters for Saccharomyces cerevisiae and other yeasts, and described carbon source inducible promoters and promoters induced by non-sugar carbon sources. A special focus is given to promoters that are activated as soon as glucose is depleted, since such promoters can be very effective and offer an uncomplicated and scalable cultivation procedure. © 2014 Weinhandl et al.; licensee BioMed Central Ltd.

Jungbauer A.,University of Natural Resources and Life Sciences, Vienna | Jungbauer A.,Austrian Center of Industrial Biotechnology
Trends in Biotechnology | Year: 2013

Continuous manufacturing has been applied in many different industries but has been pursued reluctantly in biotechnology where the batchwise process is still the standard. A shift to continuous operation can improve productivity of a process and substantially reduce the footprint. Continuous operation also allows robust purification of labile biomolecules. A full set of unit operations is available to design continuous downstream processing of biopharmaceuticals. Chromatography, the central unit operation, is most advanced in respect to continuous operation. Here, the problem of 'batch' definition has been solved. This has also paved the way for implementation of continuous downstream processing from a regulatory viewpoint. Economic pressure, flexibility, and parametric release considerations will be the driving force to implement continuous manufacturing strategies in future. © 2013 Elsevier Ltd.

Strohmeier G.A.,Austrian Center of Industrial Biotechnology | Pichler H.,Austrian Center of Industrial Biotechnology | Pichler H.,University of Graz | May O.,Royal DSM | Gruber-Khadjawi M.,Austrian Center of Industrial Biotechnology
Chemical Reviews | Year: 2011

The large number of designed enzymes successfully used in organic synthesis have shown that the application of methods and tools of mutagenesis improves the efficiency, selectivity, and stability of biocatalysts as required for certain purposes. The development of the methods is being conducted by the use of fully synthesized libraries and more efficient analytical methods and increasing knowledge of enzyme function. Research need to focus not only on designing improved enzymes but also on comprehending the effects identified. Even with limited insight into molecular mechanisms, enzymes are having a huge, positive impact on the sustainability parameters of chemical manufacturing processes. This impact will grow as the limitations of enzymes will no longer be limitations for these processes.

Hahn R.,University of Natural Resources and Life Sciences, Vienna | Hahn R.,Austrian Center of Industrial Biotechnology
Journal of Separation Science | Year: 2012

Chromatographic methods represent the most powerful techniques for purification of biopharmaceutical compounds. Quite often, the question arises which chromatographic medium should be chosen for a particular purification task or which technique should be applied to obtain the required information for a process, respectively. The present review aims to guide through these questions by presenting experimental and modeling techniques that allow a detailed characterization and comparison of chromatography media as well provide a guideline of techniques for process development. The first section provides basic information on chromatographic theory, types of chromatographic media, and different types of techniques. The second section governs description of experimental techniques including some advises for laboratory practice. The third section presents and discusses selected references from literature. Within this article, the main focus is on traditional laboratory techniques but also automated high-throughput screening methods will briefly be discussed. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fesko K.,Austrian Center of Industrial Biotechnology | Gruber-Khadjawi M.,Austrian Center of Industrial Biotechnology
ChemCatChem | Year: 2013

Carbon-carbon bond formation is among the most challenging transformations in the organic synthetic chemistry. Enzymes capable to perform this reaction are of great interest. The enzymes for stereoselective C-C bond formations have been investigated very intensively during the last two decades. New recombinant DNA technologies have paved the way for improved catalysts and broaden the application scope of the already known enzymes and reactions. On the other side new discoveries have brought more enzyme players in the arena of C-C bond formation reactions. Novel enzymatic C-C bond formation reactions have been applied, implying the most important benefit of biocatalysis, namely the high selectivity. One plus One makes One: This review describes the latest results regarding optimizations and applications of the novel as well as known enzymes for carbon-carbon bond formation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kubicek C.P.,Austrian Center of Industrial Biotechnology | Starr T.L.,University of California at Berkeley | Glass N.L.,University of California at Berkeley
Annual Review of Phytopathology | Year: 2014

Approximately a tenth of all described fungal species can cause diseases in plants. A common feature of this process is the necessity to pass through the plant cell wall, an important barrier against pathogen attack. To this end, fungi possess a diverse array of secreted enzymes to depolymerize the main structural polysaccharide components of the plant cell wall, i.e., cellulose, hemicellulose, and pectin. Recent advances in genomic and systems-level studies have begun to unravel this diversity and have pinpointed cell wall-degrading enzyme (CWDE) families that are specifically present or enhanced in plant-pathogenic fungi. In this review, we discuss differences between the CWDE arsenal of plant-pathogenic and non-plant-pathogenic fungi, highlight the importance of individual enzyme families for pathogenesis, illustrate the secretory pathway that transports CWDEs out of the fungal cell, and report the transcriptional regulation of expression of CWDE genes in both saprophytic and phytopathogenic fungi. ©2014 by Annual Reviews. All rights reserved.

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