THIS IS ACIB

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innovations from nature

science is our success



about acib The Austrian Centre of Industrial Biotechnology (acib) replaces traditional industrial processes by new, more ecological and economic methods that are adopted from nature. Therefore we connect the scientific knowledge in the field of industrial biotechnology of more than 40 researchers (at more than 10 universities) and 200 highly qualified empolyees at acib with the needs of international biotech-companies and research institutions. The centre is a competent partner for research to apply biotechnology in industrial production – focused on biocatalysis, industrially used microorganisms, synthetic biology, enzymes and (pharmaceutical) protein production and purification. acib translates academic knowledge into new industrial applications.

acib-partners get access to innovative scientific concepts, condensed academic brain power and the methodological expertise required to design unique bioprocesses and products by avoiding extensive trial & error. As part of the Austrian COMET program, we receive significant public funding for our precompetitive K2 research program. The COMET program for funding competence centers combines international spots of excellence in specific areas. It strengthens Austria as a hot spot in R&D and thus supports local as well as international companies cooperating with our competence centers.

“acib stands for industrial research integrated in the environment of more than 20 university departments.“

“acib means scientific and industrial progress through optimal cooperation.“

PROF. BERND NIDETZKY, CSO

MATHIAS DREXLER, CEO


acib at a glance new, eco-friendly, innovative and economical bioprocesses for industrial application


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facts + figures THE COMPANY

THE MISSION

acib is an international research institution with 25+ years of experience in the field of applied industrial biotechnology. 200+ employees in Austria, Germany, Italy, Spain and Czech Republic conduct 70+ scientific projects (including projects co-funded by the European Union). Combined with its key researchers and scientists at associated partners about 250 researchers collaborate within the acib network.

acib‘s intention is to discover, adopt and apply the tools and concepts of nature for industrial production processes. On the one hand we replace old industrial processes through new, greener and more economic ones, on the other we are looking for new products and opportunities for industrial production. Among others, we are searching for:

acib is owned by Graz University of Technology, Joanneum Research GmbH, University of Graz, University of Innsbruck and the University of Natural Ressources and Life Sciences Vienna. The University of Bielefeld, University of Pavia, Universitat Autonoma de Barcelona, Rzeszow Univeristy of Technology, Technical University Hamburg-Harburg, Medical University of Graz, Vienna University of Technology, FH Campus Vienna and others act as additional scientific partners. acib develops new industrial processes with more than 130 international industrial partners. acib generates new scientific knowledge within its unique strategic research program to stimulate industrial follow up projects.

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new biocatalysts new polymers engineered host cells enzymatically improved drugs continuous bioprocesses novel unit operations in downstream processing bioroutes to industrial intermediates metabolic models & modeling tools biosynthetic proteins & production cells knowledge based design tools for cell engineering and bioprocesses


industry

industrial research in academic environment

INDUSTRIAL PARTNERS 3M AB Enzymes Abitep ARA Consult Atoll Autonomous Univers. of Barcelona (AUB)* BASF Bayer Pharma BIA Separations Biotenzz Biocrates Life Sciences Bio-ferm Biomin Holding bisolbi INTER Bisy Boehringer Ingelheim RCV Carbios Chorus Clariant CNA Diagnostics DPx Fine Chemicals DSM Eli Lilly Evonik Industries Galab Laboratories Gerot Lannach – GL Pharma

Glanzstoff Industries Glaxo Smith Kline Hocus Locus inFact GesbR IPUS GmbH Janssen Pharmaceutica Jungbunzlauer KWS Saat Lactosan Lonza AG microinnova Novo Nordisk Orion Corp. Pfeifer & Langen Pfizer Ltd. pyroscience roal oy roombiotic Sandoz GmbH Sanofi Chinia Silicolife SLA SYCONIUM Synovo GmbH themis bioscience Vivimed Labs Ltd. voestalpine VTU Technology ...

SCIENTIFIC PARTNERS Austrian Institute of Technology AIT Autonomous University of Barcelona CeBiTec, University Bielefeld EMBL Heidelberg Graz University of Technology Medical University of Graz Rzeszow Univers. of Technology Technical University Hamburg-Harburg University of Applied Sciences, FH Campus Vienna University of Graz University of Innsbruck University of Ljubljana University of Nat. Resources und Life Sciences Vienna University of Pavia University of Vienna Vienna University of Technology ...

OTHER PARTNERS Biocatalysis 2021 Centre of Excellence COBIK Kakatiya Univerisity Research Centre Pharmaceutical Engineering (RCPE) Univ. of California Berkeley ...


facts + figures fields of expertise

IPR rules

Invention, prediction and design of innovative, efficient and unprecedented industrial bioprocesses based on the methods and tools of nature are core competences of acib. Cross disciplinary research involves various fields of expertise: >> host cell and vector engineering >> novel enzymes >> analytics >> protein characterization and optimisation >> novel compounds and reaction conditions >> upstream processing >> downstream processing >> bioinformatics and modeling >> synthetic pathways

acib IP rules ensure: >> a fair and clearly definded transfer and use of intellectual property (patents, secret know-how, FTO technologies with publication >> access to know how from all scientific partners by a single contract >> clearly defined rules and IP ownership before project start

benefits

>> international network of 15+ universities and 130+ companies and institutions >> exactly defined IPR rules to secure technology leadership of acib, academic & industrial partners and transfer of IP for commercialization >> forum for discussion and exchange “think-tank“ >> industrial research in an academic environment >> access to knowledge, technology and methods required in industrial biotechnology >> precompetitive basic & applied research linked to product developement & engineering which leads to an improved industrial production >> 58 % public funding of the K2 project budget

models for transfer of IP: all in: contributions for possible IPR are already included in project contributions shared scientific risk: reasonable payment at IPR creation and based on the transfer value shared economic risk: payment depends on economic success; low payment for transmission of rights and success dependent royalties how to get a project with acib

1. scientific discussion of industry with acib key researchers and CSO 2. project design between acib scientists & industry 3. entrance of company into acib consortium 4. signature of consortium agreement 5. cooperation agreement 6. IP agreement for specific project Partners from all over the world are welcome!



science at acib BiocatalySis & Enzyme technology

acib extends the search for novel reactions to replace inefficient (chemical) methodology towards still unsolved „dream-reactions“: (i) asymmetric hydration of C=C bonds, (ii) enzymatic activation of hydroxy-compounds to replace ecologically problematic Mitsunobu- and Appel-protocols, (iii) biocatalytic, metal-free replacement of the traditional Friedel-Crafts-Acylations, (iv) novel enzymatic C-C, C-S, C-O and C-N bond forming reactions. Using novel C-sources (carbohydrates, fatty acids, fermentation products) acib scientists focus on „intelligent“, highly functionalized starting materials with added value for synthesis via regio-selective enzymatic functionalization.

acib research intensifies the trend towards the development of multi-enzyme cascadereactions for the synthesis of complex organic compounds using the opportunities to employ novel chassis cells optimized in cofactor regeneration, energy and precursor generation. Of particular interest are medium-sized metabolites (C8-C14) bearing carbon atoms with varying oxidation states and a broad array of different functional groups. The incorporation of designed biocatalytic steps into existing fermentation processes at the late stage of the biosynthetic sequence will finally lead to the substitution of tedious chemical tailoring steps and to avoiding isolation of sensitive intermediates.

“acib offers the chance to submit scientific papers and to propose patents at once.“ SILVIA GLÜCK, works on enzymatic carboxylation using CO2 as carbon source


science at acib Polymer- & Environmental Biotechnology

acib’s thematic focus lies on the adaptation and application of biocatalytic processes to functionalize, modify, recycle and degrade polymers as well as on environmental biotech applications employing enzymes, living cells and also complex cell populations in biofilms – or immobilized – on mineral materials in an industrial environment. This involves the identification of novel enzymes and detailed mechanistic studies to allow a knowledge-based adaptation of these enzymes to the polymeric substrates. acib develops novel approaches in activity-based proteomics for the identification of new enzymes. This involves the establishment of a whole set of activity-based click-chemistry probes based on known covalent inhibitors specific for different enzyme classes to enable large scale discovery, substrate binding domain screening, characterization, subcellular localization and quantitative profiling of active enzymes.

The in silico screening of genomic databases and own next generation sequencing data is an another approach to identify novel enzymes acting on polymers and for polymer synthesis. The identified biocatalysts for polymer processing are then engineered for improved technological features; for example to adapt oxidoreductases to extreme environments such as for cross-linking polymers in drying films. Several projects in the area aim at developing novel approaches for enzymatic surface functionalization while others focus on recycling of polymers like polyurethanes, polyesters or polyamides, their mixtures and composites. For the environmentally and increasingly economically important biotechnical recovery of metals from waste streams acib searches for a detailed understanding of microbial interactions in biofilms that is essential for selective functional immobilization of cellular populations, especially for anaerobic and aquatic processes, that are finally able to leach metals out of waste.

“While the economic crisis still is problematic throughout Europe, Austria still offeres scientific progress.“ ENRIQUE HERRERO-ACERO, optimizes enzymatic degradation of polymers like PET, PLA and others


SYSTEMS BIOLOGY & MICROBIAL CELL FACTORIES

acib’s overall goal is the knowledge based engineering of microbial production systems for metabolites and recombinant proteins. Our challenges are to convert information from systems biological analysis and models into successful engineering strategies to adapt the cellular metabolism and its regulation efficiently for most efficient production of biomolecules. For example, we have identified negative metabolic trade off of industrial strains, which provides a framework for further targeted cell engineering, which will be a major breakthrough in further improvement of industrial processes. The challenges in heterologous protein production are still strongly found in folding and secretion of non-native proteins, limiting yields and productivities. Based on a unique extensive dataset generated at acib, we will address specific parts of the secretory pathway, which have been identified as major limiting bottlenecks. While having reached the g/L range with several complex products such as antibody Fab fragments, acib scien-

tists work on further innovative improvement by enhancing intracellular transport and oxidative folding and reducing proteolytic degradation. acib’s strategic projects are targeted towards emerging fields, namely membrane transport and artificial organelle targeting of enzymes and path-ways and non-transcriptional regulation in microbial host organisms. Metabolic Modeling

Our further goal is to rebuild nature on the computer and set up a complete mathematical model of living cells in silico. Such models are then, for instance, used to optimize the biotechnological production of value added chemicals by microorganisms. Our research focuses on mathematical modeling of the dynamics, regulation and control of metabolic networks. acib develops computational tools to predict optimized microbes for biotechnological applications.

“At acib we rely on long years of exerience around various microbial production systems and sophisticated methods of analysis.“ KRISTIN BAUMANN, designs new biotechnological production platforms


science at acib Bioprospecting & Synthetic Biology

Our vision is to combine bioprospecting and whole cell systems development with synthetic biology; including protein engineering strategies. A major long-term goal are innovative enzymes based on metal-catalysis. Fundamental research targets natural protein scaffolds in order to change their metal binding behavior and thus allows to introduce non-natural metals. An industrial goal in enzyme development is to create new and engineered whole cell biocatalysts for specific enzymatic reactions. Besides exploring the biodiversity for such enzyme systems, developing suitable engineering strategies is a highly challenging task due to the complexity of these enzyme systems. acib uses the latest methodology and strategies for screening the natural biodiversity for new interesting enzymes, novel enzyme classes, metabolic capabilities and bio-functionalities. acib’s proprietary technologies in structure based data mining and new algorithms for sequence-based computational biology are extended by implementing annotated cloud strategies. This allows more precise annotation of existing data library entries and thus the identification of new

functionalities in so far not clearly annotated sequences. The investigation of plant microbiome functions on both community and single strain level will result in concepts for a new generation of bio-based plant protection products. Synthetic Pathways

Novel chassis strains for biotransformations and novel highly valuable substances produced via incorporation of new pathways (up to 20 genes/steps) in bacteria and yeast and especially of noncanonical amino acids (NCAAs) are a priority of acib’s synthetic biology efforts. In order to gain access to the desired NCAAs for in vivo incorporation, efficient chassis strains will be generated and equipped with engineered cascade reactions or entire metabolic pathways including the introduction of specifically engineered enzymes to furnish them with the ability to biosynthesize NCAAs and their intermediates from simple precursors. The introduction of specifically engineered enzymes into the cascades and pathways will lead to the desired end products.

“acib offers a great interaction between industrial and fundamental research.“ KERSTIN STEINER, searches ways to produce amines in an eco-friendly way


Bioprocess Engineering

Engineering sciences and on fundamental aspects allow the engineering of new processes and products for bio-manufacturing. To control and monitor bioprocesses, acib addresses three goals: 1. acceleration of process development, 2. consistent quality and 3. real time release or parametric release. The latter one is subject for the future of biotech industries. Prediction of processability at a very early stage goes along with these goals. Suitable monitoring and control is a prerequisite of continuous manufacturing, which will be inverstigated by acib and implemented in the industry in the next decade.

Another goal is to answer the question if disposable materials are equivalent to conventional material/processes; this economic equation has not been solved yet. It is acib’s challenge to address the engineering and economic questions simultaneously. This has an important potential for bioprocess development and bioprocess engineering. Continuous manufacturing of bionanoparticles has not been addressed before and may be the key for satisfactory consistency, higher productivity and ready to use processes. A further challenge is to combine material science with bioprocess engineering in order to develop materials with new functions for industrial bioprocesses.

“I heard from acib and the achievements of Austrian biotechnology in Singapore.“ SIQI PAN, optimizes refolding of biotechnologically produced proteins



science at acib animal cell technology and engineering

Systems biology for mammalian production cells is the focus acib, aiming to achieve the paradigm shift from empiricism to controlling the molecular basis of productivity and product quality in mammalian cells. The establishment of bioinformatics tools, statistical analyses and mathematical models will enable the identification of relevant parameters and the prediction of cell behavior during bioprocesses, which, amongst other benefits, will lead to reduced costs for monitoring and control. As CHO production cell lines vary largely both in their genotype and phenotype, the identification of patterns of gene expression, protein activities and metabolite fluxes that correlate to process relevant properties of production cell lines, is a major goal of acib which will deliver both new engineering strategies and process monitoring protocols that focus on the state of the cells.

several challenges need to be overcome and will be addressed at acib. Improved protocols for assembly of large genomes or validated methods of model reduction for the exponentially larger metabolic models based on the high number of coding genes will be developed within acib projects. Similarly, the analysis of –omics results is more complex and interactive and thus requires new algorithms, specifically those that predict the impact of one layer of regulation on the next (eg. impact of microRNA expression on mRNA and protein concentrations). Both infrastructure and software will be provided to develop, host and maintain databases for use by researchers, the pharmaceutical industry and regulatory authorities. Finally results not covered by intellectual property rights will be made publicly accessible (www.CHOgenome.org) with a downloadable stand-alone version provided to industrial partners.

In view of the genome size of mammalian cell lines which is up to three orders of magnitude larger than that of bacteria or yeast,

“The scientific community and industry experience great enthusiasm and an athmosphere of gold rush and innovation that we live at acib.“ MARTINA BAUMANN, breaks new industrial ground using CHO cell technologies


success at acib Bodyguards for Precious Seeds

Naturally occurring bacteria as a crop protection agent are available for use in crop protection to alleviate the contamination of soil with pesticides – arguably the most environmentally friendly way of plant protection that has been developed to date.

development and optimization of the most important production cells for active agents. “Pine Aroma” against Beetles

acib researchers reduce the number of production steps from 14 to just 3 for an ecofriendly antifeedant to drive off chewing pests.

valuable synthetic biology

A new method using synthetic biology allows production of expensive grapefruit aroma Nootkatone biotechnologically from cheap sugar using a “turbo-yeast”. continuous bio-purification

Together with scientists from the University of Natural Resources Vienna we developed the world‘s first continuous purification method for valuable drugs. This will lead to cheaper pharmaceuticals that are affordable for non-privileged health care systems. „Enzym-Google“

A new search engine, including database with 100.000+ proteins opens up totally new possibilities in the search for new enzyme functions.

CO2 as a (valuable) raw material

We designed an environmentally friendly method to produce highly interesting molecules with the climate gas as a raw material for chemical synthesis. For example CO2 can now be used to produce a precursor of Aspirin. Biofuel 2.0 Without Food Use

acib explores methods which use agricultural waste, straw or resistant energy grasses as resources for new biofuels so that dugar cane, corn or other granes can be used as food rather than burning them in engines. “eco-friendly biopaints”

acib develops first biopaint by replacing potentially carcinogenic heavy metals in paints with natural enzymes (Laccases).

Microparticles as a Protein Trap

Most medicines sold today are produced biotechnologically. A new cleaning method combines five purification steps and extremely facilitates the workup process. Hamster Genome Decrypted

Sequencing of the genome of the Chinese hamster by an international research group led by acib opens up new paths in the

NEW METABOLISM IN YEAST DISCOVERED

Scientist at acib and the University of Life Sciences Vienna found duplicate copies of genes which safeguard survival of the biotech yeast Pichia pastoris in environments where only methanol is present. Find more at www.acib.at/success!


scientific contact Six research areas with 250+ scientists and key researchers allow to achieve the critical mass to invent, predict and design innovative, efficient and unprecedented industrial bioprocesses. BIOCATALYSIS & ENZYME TECHNOLOGY

BIOPROSPecTING & SYNTHETIC BIOLOGY

Key Reseachers: PROF. KURT FABER University of Graz m: kurt.faber@acib.at PROF. WOLFGANG KROUTIL University of Graz m: wolfgang.kroutil@acib.at Prof. ROLF BREINBAUER Graz University of Technology m: rolf.breinbauer@acib.at

Key Reseachers: Prof. Bernd Nidetzky Graz University of Technology m: bernd.nidetzky@acib.at PROF. GABRIELE BERG Graz University of Technology m: gabriele.berg@acib.at

POLYMER & environmental biotechnology

Key Reseacher: PROF. GEORG GĂœBITZ University of Natural Resources and Life Sciences Vienna / IFA Tulln m: georg.guebitz@acib.at SYSTEMS BIOLOGY & MICROBIAL CELL FACTORIES

Key Reseacher: PROF. DIETHARD MATTANOVICH University of Natural Resources and Life Sciences Vienna m: diethard.mattanovich@acib.at

BIOPROCESS ENGINEERING

Key Reseacher: PROF. ALOIS JUNGBAUER University of Natural Resources and Life Sciences Vienna m: alois.jungbauer@acib.at ANIMAL CELL TECHNOLOGY & ENGINEERING

Key Reseacher: PROF. NICOLE BORTH University of Natural Resources and Life Sciences Vienna m: nicole.borth@acib.at CSO

PROF. BERND NIDETZKY acib GmbH, Graz; Graz University of Technology m: bernd.nidetzky@acib.at

IMPRINT acib GmbH Petersgasse 14, 8010 Graz, Austria Pictures: istock, acib


acib GmbH head office: Petersgasse 14, 8010 Graz, Austria t: +43 316 873 9312 f: +43 316 873 9302 m: office@acib.at w: www.acib.at www.facebook.com/acibgmbh www.xing.com/companies/acibgmbh www.linkedin.com/company/acib-gmbh

The competence centre acib is funded in the framework of COMET – Competence Centers for Excellent Technologies – by BMVIT, BMWFI and the provinces of Styria, Tyrol and Vienna. The COMET programme is conducted by FFG.


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