Cofund on Biotechnologies

ANTHOcyanin production PLatform Using Suspension cultures

Project coordinator: Dr. Andrea Matros- IPK-Gatersleben - Applied Biochemistry - Germany

Project leaders:

Summary

This innovative project will produce purified anthocyanins, of varying complexity in side chain decoration, or labelled with stable isotopes as fine chemicals for assaying the composition of feedstocks for natural colours and for bioavailability, bioefficacy and mechanistic research in experimental medicine and as standards for assaying natural colorant extracts for improved formulations. The production of these new compounds from plants will span the whole of the value-chain from synthesis in novel suspension cultures, scale-up, preparative purification, assessment of bioactivities to distribution for sales.

Engineered compartments for monoterpenoid production using synthetic biology

Project coordinator: Prof. Eriko Takano - University of Manchester - UK

Project leaders:

Summary

TERPENOSOME will use synthetic biology to engineer novel organelles for the overproduction of monoterpenoids in microbial hosts. Compartmentalization will reduce side products and eliminate the toxicity problems that currently limit productivity.
TERPENOSOME will:

• Generate a portfolio of generic methods for the compartmentalization of biosynthetic pathways for bioactive molecules;
• Improve the biosynthetic enzyme systems for more efficient bioprocessing;
• Overproduce industrially relevant terpenoids, for commercialization by one of the partners.

 The generic compartmentalization methodology will be exploited by our industrial partner, Life
Technologies, in synthetic biology projects on a wide range of biotechnologically relevant high-value
compounds.

The second industry partner, ACS International, will exploit the improved production strains for the widely used precursor material limonene, as well as the two high-value compounds that are the major target molecules of TERPENOSOME.

Production of new bioactive compounds by plants and bacteria using new and improved halogenases

Project coordinator: Prof. Karl-Heinz van Pee - TU Dresden - Germany

Project leaders:

Summary

The in vitro use of halogenases is hampered by a fast inactivation of the enzymes under reaction conditions. To allow the use of halogenases in biotechnological processes, the reason for inactivation will be elucidated and stabel halogenase variants will be constructed. Since their application is also restricted by the high substrate specificity variants with a relaxed substrate specificity will be constructed. Already available tryptophan halogenases and variants from the project will be used to transform plants and bacteria producing tryptophan-containing secondary metabolites or indole derivatives to obtain new halogenated compounds produced in vivo. Using mild chemistries, the halogen atoms can be exchanged against different functional groups leading to novel compounds. Cultivation of transformed plants producing novel halogenated compounds will be optimised, the metabolic profile analysed and the biological and antioxidant activities of the compounds will be investigated.

Investigating NOvel VAluable bio-Therapeutics and Expression systems

Project coordinator: Prof. Christopher Mark Smales - University of Kent - UK

Project leaders:

Summary

The production of IgGs has revolutionized the biotech industry with products used for the treatment of cancer and immune disorders. IgGs represent just one potential class of biotherapeutic and yet few other classes (with potential to treat specific diseases) have been as well developed due to challenges in their manufacture. Challenging new recombinant proteins (rPs) of commercial and clinical value include fusion proteins (for novel disease targeting), IgA (the most abundant Ig isoform, for treatment of IgA deficiencies, cancer) and secreted mucins (for disease therapy, vaccines). This project will develop new animal (CHO) and plant (tobacco) cell and glycosylation expression technologies, and establish bioprocesses, for the production of these difficult to express novel rPs that have the potential to open up new targets and treatments that resist current therapies. The consortium will seek protection of IP rights for the new technologies and to develop these with interested parties.

Recovery of high value Proteins from Serum by innovative direct Capture techniques

Project coordinator: Prof. Matthias Franzreb - Karlsruhe Institue of Technology, Eggenstein-Leopoldshafen - Germany

Project leaders:

Summary

The extraction of biopharmaceuticals from natural sources often employs overly complicated antiquated procedures. The downstream processing of serum is a case in point; it comprises large numbers of steps of low purification power and consequently delivers poor overall product yields.

Parallel advances in magnetic separation equipment and approaches to manufacture magnetic affinity particles, funded through several national and EU funded projects lay the foundations for the proposed work. Using magnetic bioseparation techniques, the consortium will seek to replace outdated organic solvent based fractionation methods, which can inflict serious damage on especially prone protein targets.

In ProSeCa, our combined expertise will be applied to the production of protein based veterinary medicines from horse sera, centring on harmonious integrated use of: highly selective magnetic adsorbents manufactured via: (i) chemical; (ii) biological; and (iii) mixed ‘biological/chemical’ routes; with a fully automated and cGMP compliant magnetic separator.

Integrated Platform for de novo Design and Development of a Chimeric Enzyme for high-value chemicals

Project coordinator: Dr. Ricardo Jorge Flores Branco - Fac. Sci. and Tech., Universidade nova de Lisboa, Caparica - Portugal

Project leaders:

Summary

The CHImerASE project intends to develop a platform for the design of chimeric enzymes applied to new biotransformation steps. The team aims to deliver an efficient de novo designed enzyme to accomplish a high value industrial transformation that is currently only accessible via a laborious conventional chemical process. The consortium partners strongly believe that such innovative approach will represent a breakthrough in the biocatalysis field with a significant impact at industrial, economic and environmental levels.

The multilateral consortium was set up based on the complementary expertise of three academic and non-profit research institutions, a world's leading chemical company which has a top market position in speciality chemicals manufacture and delivery, as well as unique know-how in biotech technology transfer and industrial process scale-up, and a SME biotech with consulting and manufacturing experience of engineered enzymes, resulting in a transnational cooperation between Austria, Germany and Portugal.

Novel carbohydrate modifying enzymes for fibre modification

Project coordinator: Mr. Matti Siika-aho - VTT Technical Research Centre of Finland, Espoo - Finland

Project leaders:

Summary

The overall objective of the ELMO project is to provide new enzyme products for the needs of the pulp and paper industry, especially for modification of dissolving grade pulps. As a result of the project, more efficient enzyme products for pulp modification will be made available for industrial production. The developed pulp treatments with the novel enzymes enable activation of pulp cellulose, thus enhancing pulp dissolution, decreasing hemicellulose content of dissolving pulps and improving pulp refining processes.

Scientifically, the action of enzymes on cellulosic substrates will be characterized and their effects on fibres studied using advanced analytical tools. The obtained understanding makes it possible to further develop novel and more targeted enzyme tools. The enzymes developed in the project can also find applications in other industries dealing with cellulosic raw materials, such as textile, biorefinery and biofuel industry as well as food and feed processing.

Designer yeast strain library optimized for metabolic engineering applications

Project coordinator: Dr. Kiran Raosaheb Patil - European Molecular Biology Laboratory, Heidelberg - Germany

Project leaders:

Summary

Saccharomyces cerevisiae is one of the most widely used cell factories in industrial biotechnology. Moreover, several novel biosustainable processes using S. cerevisiae that are today under development have the potential to replace traditional petro-chemical synthesis. However, the development of optimized cell factories for the production of novel compounds is a time-consuming process and represents a significant cost/time burden. DeYeastLibrary project will help overcoming this hurdle by using cutting-edge computational and experimental tools. The project will exploit the biochemical design principles of nature for constructing a pre-optimized library of platform strains with improved precursor supply, which will accelerate the development of yeast-based bioprocesses. In the DeYeastLibrary project, these platform strains will find application in creating more efficient cell factories for sustainable production of vanillin, poly-hydroxy butyrate (PHB), n-butanol and succinic acid.

Integrated Process and Cell Refactoring Systems for Enhanced Industrial Biotechnology

Project coordinator: Dr. Darren Nesbeth - University College London - UK

Project leaders:

Summary

Valorisation of low-value waste glycerol could transform the economics of biodiesel production.Key challenges for achieving this with biocatalysis are the rate of glycerol conversion to products, integrating bioprocess steps and tolerance of crude feedstock contaminants by host strains.

We are industrial and academic bioprocess, cell-engineering, omics and bio-systems specialists. We will port pathways into Saccharomyces cerevisiae and Pichia pastoris for production of two valuable compounds from glycerol: chiral amino-alcohols (CAA) and 1,2-propanediol (PDO).

Cells will be characterised with high throughput micro-scale process techniques and at scale. Transcriptomic and metabolomic data will be combined with process insights to dictate refactoring of both pathways and host 'chassis'. These steps will be repeated for second-iteration cells, driving better performance. New strains, processes and integrated methods will be of use to biodiesel and Industrial Biotechnology sectors.