innovationsfromnature

science is our success

about acibacib-partners get access to innovative scien-tific 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 compe-tence centers combines international spots of excellence in specific areas. It strengthens Austria as a hot spot in R&D and thus sup-ports local as well as international com-panies cooperating with our competence centers.

The Austrian Centre of Industrial Biotechno-logy (acib) replaces traditional industrial pro-cesses by new, more ecological and econo-mic methods that are adopted from nature.

Therefore we connect the scientific know-ledge 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 inter-national biotech-companies and research institutions.

The centre is a competent partner for re-search to apply biotechnology in industrial production – focused on biocatalysis, indus-trially used microorganisms, synthetic bio-logy, enzymes and (pharmaceutical) protein production and purification. acib translates academic knowledge into new industrial applications.

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

MATHIAS DREXLER, CEO

“acib stands for industrial research integrated in the environment of more than 20 university departments.“PROF. BERND NIDETZKY, CSO

new,eco-friendly,innovative and economicalbioprocesses for industrial application

acib at a glance

stat

istic

s and

adv

ance

d da

ta h

andl

ing

enzymes & polymerssynthetic biology

molecular, stru

ctural & cell b

iology

site d

irect

ed m

utag

enes

is

metabolite production

expression systems

fungi & animal cell lines

biocatalyst imm

obilizationm

icroorganisms

biopharmaceutical technologies

biocatalysis in organic synthsis

whole cell biotransformation

bioprotection

genom

ics, m

etab

olom

ics, p

rote

omics

met

abol

ic m

odel

ing,

bio

info

rmat

ics

acib at a glance

screening & isolation of

dire

cted

evo

lutio

n,

purificationenzym

ology, enzyme production &

engineeringferm

entation & bioprocess

pure compoundssynthesis of enantiomeric

throughput screening

assay developement, high

process optimization

reaction engineering &

researchers collaborate within the acib network.

THE MISSION 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 proces-ses through new, greener and more eco-nomic ones, on the other we are looking for new products and opportunities for in-dustrial production. Among others, we are searching for:

> 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

THE COMPANY

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 is owned by Graz University of Techno-logy, Joanneum Research GmbH, Universityof 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 Technolo-gy, Technical University Hamburg-Harburg, Medical University of Graz, Vienna Univer-sity of Technology, FH Campus Vienna and others act as additional scientific partners.

acib develops new industrial processes with more than 130 international industrial part-ners.

acib generates new scientific knowledge within its unique strategic research program to stimulate industrial follow up projects.

facts + figures

industrial researchin academic environment

industry

INDUSTRIAL PARTNERS3MAB EnzymesAbitepARA ConsultAtollAutonomous Univers. of Barcelona (AUB)*BASFBayer PharmaBIA SeparationsBiotenzzBiocrates Life SciencesBio-fermBiomin Holdingbisolbi INTERBisyBoehringer Ingelheim RCVCarbiosChorusClariantCNA DiagnosticsDPx Fine ChemicalsDSMEli LillyEvonik IndustriesGalab LaboratoriesGerot Lannach – GL Pharma

Glanzstoff IndustriesGlaxo Smith KlineHocus LocusinFact GesbRIPUS GmbHJanssen PharmaceuticaJungbunzlauerKWS SaatLactosanLonza AGmicroinnovaNovo NordiskOrion Corp.Pfeifer & LangenPfizer Ltd.pyroscienceroal oyroombioticSandoz GmbHSanofi ChiniaSilicolife SLASYCONIUMSynovo GmbHthemis bioscienceVivimed Labs Ltd.voestalpineVTU Technology...

SCIENTIFIC PARTNERSAustrian 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 PARTNERSBiocatalysis 2021Centre of Excellence COBIKKakatiya UniverisityResearch Centre Pharmaceutical Engineering (RCPE)Univ. of California Berkeley...

IPR RULES

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

models for transfer of IP:all in: contributions for possible IPR are already included in project contributionsshared scientific risk: reasonable payment at IPR creation and based on the transfer valueshared 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 consor-tium

4. signature of consortium agreement5. cooperation agreement6. IP agreement for specific project

Partners from all over the worldare welcome!

FIELDS OF EXPERTISE

Invention, prediction and design of inno-vative, efficient and unprecedented indus-trial 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 condi-

tions > upstream processing > downstream processing > bioinformatics and modeling > synthetic pathways

BENEFITS

> international network of 15+ universities and 130+ companies and institutions

> exactly defined IPR rules to secure tech-nology leadership of acib, academic & industrial partners and transfer of IP for commercialization

> forum for discussion and exchange - “think-tank“

> industrial research in an academic envi-ronment

> access to knowledge, technology and methods required in industrial biotech-nology

> precompetitive basic & applied research linked to product developement & engineering which leads to an improved industrial production

> 58 % public funding of the K2 project budget

facts + figures

science at acib

“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

acib extends the search for novel reactions to replace inefficient (chemical) methodolo-gy towards still unsolved „dream-reactions“: (i) asymmetric hydration of C=C bonds, (ii) enzymatic activation of hydroxy-compounds to replace ecologically problematic Mitsu-nobu- and Appel-protocols, (iii) biocatalytic, metal-free replacement of the traditional Friedel-Crafts-Acylations, (iv) novel enzy-matic 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 syn-thesis via regio-selective enzymatic functio-nalization.

BIOCATALYSIS & ENZYME TECHNOLOGY

acib research intensifies the trend towards the development of multi-enzyme cascade-reactions for the synthesis of complex or-ganic compounds using the opportunities to employ novel chassis cells optimized in cofactor regeneration, energy and precursor generation. Of particular interest are medi-um-sized metabolites (C8-C14) bearing car-bon 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 iso-lation of sensitive intermediates.

science at acib

“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

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 bio-tech applications employing enzymes, living cells and also complex cell populations in biofilms – or immobilized – on mineral mate-rials in an industrial environment.

This involves the identification of novel enzy-mes and detailed mechanistic studies to al-low a knowledge-based adaptation of these enzymes to the polymeric substrates. acib develops novel approaches in activity-based proteomics for the identification of new en-zymes. 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 ena-ble large scale discovery, substrate binding domain screening, characterization, subcel-lular 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 poly-mer synthesis. The identified biocatalysts for polymer processing are then engineered for improved technological features; for examp-le to adapt oxidoreductases to extreme envi-ronments such as for cross-linking polymers in drying films.

Several projects in the area aim at develo-ping novel approaches for enzymatic sur-face functionalization while others focus on recycling of polymers like polyurethanes, polyesters or polyamides, their mixtures and composites. For the environmentally and increasingly economically important biotech-nical recovery of metals from waste streams acib searches for a detailed understanding of microbial interactions in biofilms that is essential for selective functional immobili-zation of cellular populations, especially for anaerobic and aquatic processes, that are finally able to leach metals out of waste.

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 ad-apt the cellular metabolism and its regulati-on efficiently for most efficient production of biomolecules. For example, we have iden-tified negative metabolic trade off of indus-trial strains, which provides a framework for further targeted cell engineering, which will be a major breakthrough in further improve-ment of industrial processes.

The challenges in heterologous protein pro-duction 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 pa-thway, 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-

SYSTEMS BIOLOGY & MICROBIAL CELL FACTORIES

“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

tists work on further innovative improvement by enhancing in-tracellular transport and oxidative folding and reducing proteolytic de-gradation. 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 mathema-tical model of living cells in silico. Such mo-dels are then, for instance, used to optimize the biotechnological production of value ad-ded chemicals by microorganisms.Our research focuses on mathematical mo-deling of the dynamics, regulation and con-trol of metabolic networks. acib develops computational tools to predict optimized microbes for biotechnological applications.

science at acib

Our vision is to combine bioprospecting and whole cell systems development with syn-thetic biology; including protein engineering strategies. A major long-term goal are in-novative enzymes based on metal-catalysis. Fundamental research targets natural prote-in scaffolds in order to change their metal binding behavior and thus allows to introdu-ce non-natural metals. An industrial goal in enzyme development is to create new and engineered whole cell biocatalysts for spe-cific enzymatic reactions. Besides exploring the biodiversity for such enzyme systems, developing suitable engineering strategies is a highly challenging task due to the comple-xity of these enzyme systems.

acib uses the latest methodology and stra-tegies for screening the natural biodiversity for new interesting enzymes, novel enzyme classes, metabolic capabilities and bio-func-tionalities. acib’s proprietary technologies in structure based data mining and new algo-rithms for sequence-based computational biology are extended by implementing an-notated cloud strategies. This allows more precise annotation of existing data library entries and thus the identification of new

BIOPROSPECTING & SYNTHETIC BIOLOGY

“acib offers a great interaction between industrial and fundamental research.“

KERSTIN STEINER, searches ways to produce amines in an eco-friendly way

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

Synthetic Pathways

Novel chassis strains for biotransformations and novel highly valuable substances pro-duced 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, ef-ficient chassis strains will be generated and equipped with engineered cascade reac-tions or entire metabolic pathways including the introduction of specifically engineered enzymes to furnish them with the ability to biosynthesize NCAAs and their intermedia-tes from simple precursors. The introduction of specifically engineered enzymes into the cascades and pathways will lead to the desi-red end products.

BIOPROCESS ENGINEERING

“I heard from acib and the achievements of Austrian biotechnology in Singapore.“

SIQI PAN, optimizes refolding of biotechnologically produced proteins

Engineering sciences and on fundamental aspects allow the engineering of new pro-cesses and products for bio-manufacturing. To control and monitor bioprocesses, acib addresses three goals:

1. acceleration of process development,2. consistent quality and3. real time release or parametric release.

The latter one is subject for the future of biotech industries. Prediction of processa-bility at a very early stage goes along with these goals. Suitable monitoring and control is a prerequisite of continuous manufactu-ring, which will be inverstigated by acib and implemented in the industry in the next de-cade.

Another goal is to answer the question if disposable materials are equivalent to con-ventional 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 deve-lopment and bioprocess engineering. Con-tinuous 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.

science at acib

“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

ANIMAL CELL TECHNOLOGY AND ENGINEERING

Systems biology for mammalian production cells is the focus acib, aiming to achieve the paradigm shift from empiricism to control-ling the molecular basis of productivity and product quality in mammalian cells. The es-tablishment of bioinformatics tools, statisti-cal analyses and mathematical models will enable the identification of relevant para-meters and the prediction of cell behavior during bioprocesses, which, amongst other benefits, will lead to reduced costs for moni-toring and control.

As CHO production cell lines vary largely both in their genotype and phenotype, the identification of patterns of gene expressi-on, 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.

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

several challenges need to be overcome and will be addressed at acib. Improved proto-cols for assembly of large genomes or vali-dated 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 re-quires new algorithms, specifically those that predict the impact of one layer of regu-lation on the next (eg. impact of microRNA expression on mRNA and protein concentra-tions). Both infrastructure and software will be provided to develop, host and maintain databases for use by researchers, the phar-maceutical industry and regulatory authori-ties. Finally results not covered by intellec-tual property rights will be made publicly accessible (www.CHOgenome.org) with a downloadable stand-alone version provided to industrial partners.

success at acibBODYGUARDS FOR PRECIOUS SEEDSNaturally occurring bacteria as a crop pro-tection agent are available for use in crop protection to alleviate the contamination of soil with pesticides – arguably the most envi-ronmentally friendly way of plant protection that has been developed to date. VALUABLE SYNTHETIC BIOLOGYA new method using synthetic biology al-lows production of expensive grapefruit aroma Nootkatone biotechnologically from cheap sugar using a “turbo-yeast”. CONTINUOUS BIO-PURIFICATIONTogether with scientists from the University of Natural Resources Vienna we developed the world‘s first continuous purification me-thod for valuable drugs. This will lead to che-aper 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. MICROPARTICLES AS A PROTEIN TRAPMost medicines sold today are produced biotechnologically. A new cleaning method combines five purification steps and extre-mely facilitates the workup process.

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

development and optimization of the most important production cells for active agents. “PINE AROMA” AGAINST BEETLESacib researchers reduce the number of pro-duction steps from 14 to just 3 for an eco-friendly antifeedant to drive off chewing pests. CO2 AS A (VALUABLE) RAW MATERIALWe designed an environmentally friendly method to produce highly interesting mole-cules with the climate gas as a raw material for chemical synthesis. For example CO2 can now be used to produce a precursor of As-pirin. BIOFUEL 2.0 WITHOUT FOOD USEacib explores methods which use agricultu-ral 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 po-tentially carcinogenic heavy metals in paints with natural enzymes (Laccases).

NEW METABOLISM IN YEAST DISCOVEREDScientist at acib and the University of Life Sciences Vienna found duplicate copies of genes which safeguard survival of the bio-tech yeast Pichia pastoris in environments where only methanol is present.

Find more at www.acib.at/success!

BIOPROSPECTING &SYNTHETIC BIOLOGYKey Reseachers:PROF. BERND NIDETZKYGraz University of Technologym: bernd.nidetzky@acib.atPROF. GABRIELE BERGGraz University of Technologym: gabriele.berg@acib.at

BIOPROCESS ENGINEERINGKey Reseacher:PROF. ALOIS JUNGBAUERUniversity of Natural Resources andLife Sciences Viennam: alois.jungbauer@acib.at

ANIMAL CELL TECHNOLOGY & ENGINEERINGKey Reseacher:PROF. NICOLE BORTHUniversity of Natural Resources andLife Sciences Viennam: nicole.borth@acib.at

CSOPROF. BERND NIDETZKYacib GmbH, Graz;Graz University of Technologym: bernd.nidetzky@acib.at

BIOCATALYSIS &ENZYME TECHNOLOGYKey Reseachers:PROF. KURT FABERUniversity of Grazm: kurt.faber@acib.atPROF. WOLFGANG KROUTILUniversity of Grazm: wolfgang.kroutil@acib.atProf. ROLF BREINBAUERGraz University of Technologym: rolf.breinbauer@acib.at

POLYMER & ENVIRONMENTALBIOTECHNOLOGYKey Reseacher:PROF. GEORG GÜBITZUniversity of Natural Resources andLife Sciences Vienna / IFA Tullnm: georg.guebitz@acib.at

SYSTEMS BIOLOGY & MICROBIAL CELL FACTORIESKey Reseacher:PROF. DIETHARD MATTANOVICHUniversity of Natural Resources andLife Sciences Viennam: diethard.mattanovich@acib.at

scientific contact

IMPRINT

acib GmbH

Petersgasse 14, 8010 Graz, Austria

Pictures: istock, acib

Six research areas with 250+ scientists and key researchers allow to achieve the critical massto invent, predict and design innovative, efficient and unprecedented industrial bioprocesses.

acib GmbHhead office: Petersgasse 14, 8010 Graz, Austriat: +43 316 873 9312f: +43 316 873 9302m: office@acib.atw: 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.