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Technology

Industrial biotechnology

Industrial Biotechnology is the use of natural processes - primarily of enzymes and microbial cells - for industrial manufacturing. It is also known as "white biotechnology”, in distinction from "red biotechnology”, which is devoted to medical and pharmaceutical purposes, and "green biotechnology”, or the application of biotechnology in agriculture.

Based on the use of enzymes, the white biotechnology industry manufactures products with a distinct market value worldwide and shows sustained annual growth rates. EUCODIS Bioscience serves this market by providing novel and customized enzyme solutions tailored to perform in challenging industrial applications in pharma, cosmetics, food & feed, and fine chemistry.

White biotechnology is considered a key technology of the 21st century, as it offers sustainable aspects by offering economical and environmental advantages over traditional chemistry:

Lower energy consumption

Enzymes enable chemical reactions at lower "biological" temperatures, as opposed to high temperatures often required in traditional chemistry, significantly reducing energy consumptions.

Replacing complex syntheses and purifications

Highly selective enzymes permit the manufacture of chiral compounds and other difficult-to-synthesize intermediates, e.g. for the production of active pharmaceutical ingredients (APIs) with less side-products compared to conventional synthesis steps. This helps to reduce waste and decreases the need for purification of the reaction products. Customized enzymes help the chemical industry replace complex synthesis steps by a simple biocatalytic reaction, making their products and processes more competitive.

Renewable resources

Enzymes play a key role in worldwide strategies for the production of high-value bioproducts, chemical building blocks, and bioenergy from renewable resources. Making biomass and biotechnology an alternative to petroleum based products benefits the environment and spurs economic growth.

Enzymatic protein drug conjugation (CTATTM)

This novel, patented linker technology is designed to covalently attach a payload molecule to a recombinant antibody, antibody fragment or protein through a site-specific enzymatic reaction. The payload molecule can be a therapeutic drug molecule, a dye for diagnostics or e.g. a PEG molecule to increase the stability and half-life of a therapeutic protein.

The CTATTM enzyme recognizes a short sequence of three amino acids at the C-terminus of the antibody/protein to be conjugated. This unique target sequence is easily introduced to an antibody by an expression plasmid. The CTATTM enzyme cuts at this specific target site and covalently links the payload molecule to the antibody. This directed conjugation approach is not interfering with the antigen binding site or the structure of the antibody.

Benefits

  • Site specific modification: No interference with antigen binding site, structural integrity of the antibody/(sc)FAB maintained.
  • Covalent conjugation by formation of a peptide bond: Stable covalent linkage between antibody and drugs, dyes, beads, matrices and surfaces.
  • Controlled conjugation resulting in a specific payload-antibody ratio: Optimal for specific drug delivery or diagnostic quantification of antigens.
  • Short recognition sequence: Minimal linker sequence between label and conjugated protein is optimal for low immunogenicity but can be extended to carry more drugs if needed for the application.
  • Cleavage possible: Enzymatic removal of conjugate is possible if wanted.

Applications

  • Antibody-drug conjugates (ADCs): functionalizing of antibodies for therapeutic applications like targeted delivery of potent cytotoxic agents.
  • Labeling of recombinant proteins, antibodies or antibody fragments for fluorescence microscopy, flow cytometry, or antibody-based assays (ELISA).
  • Covalent, directional immobilization on beads, matrices, columns.

FIND OUT MORE

The CTATTM-technology is available for licensing on target basis or as a whole. EUCODIS Bioscience is also interested in co-development partners. Please contact our business development team.

Protein engineering technologies

EUCODIS Bioscience applies state-of-the-art protein engineering technologies to improve parameters like activity, stability or substrate selectivity of the target enzymes. Besides more common technologies like random mutagenesis, site-directed mutagenesis or site saturation mutagenesis for directed evolution of enzymes, EUCODIS Bioscience has additionally developed proprietary gene shuffling and in vivo recombination technologies to increase biodiversity and obtain high performance biocatalysts.

In vivo recombination exploits the industrial potential of recombination in living cells through the precise control of the DNA Mismatch Repair System. This tool represents a versatile and powerful technology for the development of enzymes optimized for specific industrial applications.

In a natural environment only similar (homologue) DNA sequences can be recombined. The DNA Mismatch Repair System prevents recombination between diverged DNA sequences, such as sequences from different species. Our technology allows to selectively switch off this control mechanism in organisms such as yeast or bacteria, enabling the recombination of variants of a gene with only 65 percent homology.

The key advantage of our technology is its efficacy. Already after the first round of recombination, our technology generates high-quality libraries of mosaic genes or operons, consisting only of true recombinants. A high proportion of novel enzymes created with this technology are functional, because crossovers only occur at sequence-defined domains.

Moreover, no frame-shifts, stop codons, insertions or deletions are generated, leaving the integrity of the tertiary protein structure undisturbed. The resulting recombinants are then screened to identify genes encoding enzymes with novel or improved functions.

FIND OUT MORE

For detailed information on our in vivo recombination technology, please contact Dr. Jan Modregger, Head of Research and Development  >

Biofermentation

The term “biofermentation” describes a broad range of technologies for the environmentally friendly production of smaller molecules by fermentation processes. Microbial or fungal cells are used to convert substrate molecules into product molecules of higher value, or microbial cells are genetically engineered and modified to produce novel molecules from cost-efficient renewable feedstocks (“cell factories”).

EUCODIS Bioscience has a long history of genetically engineering cells by manipulation of the cellular metabolism and by introduction of novel enzymes and biocatalytic pathways to generate such cell factories. We offer to identify and optimize enzymes for your cell factory, or to develop microbial production strains and processes for the production of your target molecules as service.

FIND OUT MORE

Read more about Biofermentation

Immobilization

Immobilization of biocatalysts has many benefits over free biocatalysts:

  • It allows the repeated use and recycling of the biocatalysts to decrease process costs,
  • It often stabilizes sensitive enzymes for reactions in organic solvents or at higher temperatures,
  • It can be used to pack biocatalysts into flow or column reactors for highest process yields.

The biocatalysts selected for our customers can be immobilized by different techniques, e.g. by adsorption or though covalent chemical bonds. Furthermore, supporting resins can be modified for specific reaction environments, e.g. configuring the surface more or less hydrophobic or hydrophilic. EUCODIS Bioscience works closely with Resindion, a manufacturer of various immobilization resins, to provide optimal immobilized biocatalyst solutions for your application.

EUCODIS Bioscience not only provides several of its enzymes in immobilized forms off the shelf (e.g. immobilized lipases), but also offers to develop customized immobilized biocatalysts as a service.

Environmental monitoring

Microbial environmental monitoring is important for industrial processes and in health care when products and facilities have to be proven to be free of microbial contaminations, e.g. in pharma and food production or in hospitals. The cleaning and disinfection of these facilities is monitored using microbial growth media, and EUCODIS Bioscience offers different enzymes as additives to such media to make the detection of contaminants easier and safer.

EUCODIS LacBusterTM beta-lactamases are used worldwide in agar plates for the neutralization of beta-lactam antibiotics, and are e.g. used for the determination of microbial contaminations in beta-lactam production sites by effectively inactivating residual antibiotics present in the production area, thus enabling growth of contaminants. EUCODIS Bioscience offers beta-lactamases not only for incorporation in agar plates, but also for liquid growth media used in sterility tests according to the various Pharmacopoeiae (Ph. Eur., USP, etc.). Ready-made agar plates are also available directly from EUCODIS Bioscience or through international distributors.

EUCODIS Catalase is a novel patented enzyme technology used for the neutralization of hydrogen peroxide in liquid or solid media. Hydrogen peroxide is more and more used as universal, environmentally friendly disinfection reagent, but remaining traces make the detection of surviving contaminants difficult. Our EUCODIS Catalase offers superior activity and stability compared to other neutralizing agents, especially at high hydrogen peroxide concentrations, and withstands sterilization of prepared media by gamma-irradiation. It is available directly from EUCODIS Bioscience.

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