The broad range of scientific excellence at acib is divided in 12 research fields,covering all sectors of industrial biotechnology.
Biotransformation for synthesis
In the research field biotransformation for synthesis, biocatalysts are used to convert and synthesize molecules. Biocatalysts enable us to replace inefficient, chemical methods by more environmentally friendly processes. Biocatalytic reactions feature a number of advantages: They usually need mild process conditions (neutral pH, normal air pressure and gentle temperatures between 20 and 45°C as well as aqueous buffer systems), are working without toxic heavy metals and are then highly efficient in fast conversions, chemo-, regio- and stereoselectivity. In order to use biocatalysis in as many reactions as possible, there is an increasing need for new enzymes for technological applications (e.g. for the production of pharmaceuticals, fine chemicals, agrochemicals, food).
acib focuses on new innovative biocatalytic reactions, studying new enzymes and reactions on a molecular level in order to successfully establish enhanced bioprocesses.
Biotechnological material processing
Biotechnological material processing is becoming more and more important in the circular economy and is a meaningful part of biorefineries for the use of renewable resources. The advantage of biotechnological conversions is not only mild process conditions but also their high specificity. Acib aims at developing new biotechnological approaches for specific demands within different value chains. For example, new biotechnological solutions help to provide natural and synthetic materials with specific attributes. In terms of synthetic materials, acib researchers focus on the investigation of biobased and biodegradable polymers, including the development of biotechnological recycling procedures of polymer building blocks and even valuable metals. In the sense of a sustainable production new approaches for the conversion of CO2 into platform chemicals are explored.
Recombinant protein production
acib focuses on the improvement and optimization of prevalent cell factories Escherichia coli (the most frequently used bacterial system), Pichia pastoris (yeast) and Trichoderma reseei (filamentous fungi). The main objective of the research activities are to foster an understanding of the molecular, genetic and regulatory mechanisms, that enable the cells to survive in current bioprocess conditions with high cell density and yield and to perform reliably and reproducibly. The knowledge gained will be used for a facilitated selection of appropriate cell lines (screening), for adjusting cell lines to current demands by alterations in gene expression and for adapting bioprocesses for optimal conditions in order to allow cells to perform reproducibly (bioprocess optimization).
Metabolic modelling and engineering
Metabolic engineering is an applied research field aiming at a targeted modification of metabolic pathways in microorganisms in order to allow the production of high yields (e.g small organic compounds). acib works on the improvement and optimization of yeast and filamentous fungi for the overproduction of organic acids. A comprehensive understanding of the molecular, genetic and regulatory mechanisms for the overproduction of these compounds is necessary to obtain highly productive strains (cell engineering). Based on that, bioprocesses can be adapted for optimal production conditions.
Modelling of cellular systems and systems biology
Systems biology is a cross-sectional discipline that plays an important role in many projects. In this research area, acib focusses on the mathematic metabolic modelling of biotechnologically relevant cells. The main objective is the integration of experimental data about cellular metabolic regulations into the youngest generation of metabolic models of acib’s most relevant workhorses Pichia pastoris and Saccharomyces cerevisiae. Another objective is the integration of systems biological data (gene regulations, proteins, measurable metabolic products) in order to obtain new findings for the development of new production platforms.
Enzyme and protein engineering
Enzymes are highly efficient catalysts for chemical transformations. This research topic focuses on the identification, design, development, utilization and targeted improvement of enzymes for technological applications, especially in the industry. The integrative development of robust biocatalysts in technical processes and of functional proteins without catalytic activity are main objectives and are expected to be applied in material sciences, analytics and medical sciences. The development of new enzymes and proteins is based on a multidisciplinary approach that includes molecular and process relevant aspects. Tailored enzymes used as biocatalysts and as products for analytics and diagnostics are interesting research topics of this field.
In the area bioprospecting, the investigation of new microbiomes and microorganisms and their spectrum of metabolites is supposed to lead to potential new biotechnological applications. Microbiome research is a rather new discipline. In recent years, it has become obvious that a balanced microbiome is an important factor for each organism’s health. acib develops biotechnological products that can recover this fragile balance and protect culture plants from biotic and abiotic stress. Apart from that, acib explores metabolic interactions in order to identify new, bioactive substances.
Continuous integrated manufacturing
Currently, the preferred production route in the biopharmaceutical industry is a batch process. Due to high costs and governmental regulations there is a demand for continuous production processes. However, the scientific background is limited. acib has identified this demand and established a research focus addressing this dilemma. acib aims at developing continuous processes in lab scale and complement this with basic research, in order to transform current batch processes into continuous approaches. Thus, acib-researchers are presently developing an “in-process control” for monitoring particular production steps, continuous processes for the production of recombinant coagulation proteins and continuous and integrated production processes for viruses and virus-like particles.
New materials for bioprocessing
The use of new materials in existing processes can lead to new functions or substantial improvements of the processes. Currently, there are hardly any processes for the purification of bionanoparticles . Thus we strive for new materials, which are highly porous and recognize particles by their geometric forms. Fractal structures with the named attributes are obtained by crystallization of metal oxides (e.g. titan oxide). Nanomembranes are developed, which allow transport against the concentration gradient. For the regeneration of cofactors needed for the active transport, membranes are coated with gold nanoparticles providing conductibility. For the active transport, acib uses special transporters such as xylosetransporters.
New processes for biopharmaceuticals
acib focuses on intensified biotechnological processes and process understanding in this research areas. A basic mechanistic process understanding is also required by pharma authorities. The objectives are reliable predictions from smallest chromatography columns up to large scale equipment for the purification of biopharmaceuticals and the optimization of production processes by high-throughput approaches, e.g. for the production of biopharmaceuticals in E. coli, which usually are not very stable. In addition we produce enzymes to be used for the purification of biopharmaceuticals, which perfectly complements the activities within this research field.
Genome information databases for CHO
Knowledge about genomic sequences of the most relevant biotechnological workhorses such as Escherichia coli or Saccharomyces cerevisiae was available very early. In contrast, the genome of Chinese Hamster Ovary cells (CHO) has been resolved and published quite recently (between 2011 and 2013) with acib being part of this research. The CHO cell line is currently used for the production of 8 out of the top 10 blockbuster biotherapeutic agents and, thus, is extremely relevant for industrial applications. Knowing the gene sequence is essential in order to further improve and facilitate the production of biopharmaceuticals, and make them cheaper. The objective of this research focus is the extension and exploration of data sets and models to improve production efficiency and efficacy.
Cell line engineering
This research field focuses on the improvement of CHO cell factories in terms of growth rate (with a high yield of biomass the yield of biotherapeutics also increases), productivity and product quality. These aspects demand for a detailed analysis of cell behaviour with different properties on transcriptomic and proteomic level in order to identify limiting processes. These processes are engineering targets, so that efficiency and yield can be increased in industrial production processes. The methods of choice are either genetic engineering (insertion of additional “missing” genes, overexpression) or the development of effective selective methods.