Delft, Netherlands
Delft, Netherlands

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Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE-2009-3-3-02 | Award Amount: 3.47M | Year: 2010

This project intends to engineer transaminase libraries that will be applied as the main enzymatic technology to deliver the amine functionality in the commercially valuable products of both chiral and bulk amine targets. These enzymes will be used in enzymatic cascades where simple starting materials are converted into the required intermediates for transamination or further enzymatic steps will be used to remove products from the transaminase reaction which will add value by extra functionality. This will also be supported by the development of enzymatic cascades to deliver efficient co-factor recycling and achieve the high conversions required for industrial use. A high throughput screening method based on a further enzymatic cascade will be developed. Engineering solutions will be used to overcome obstacles associated with the implementation of this core technology on a larger scale and integrate the use of other enzymes into the synthetic pathway to allow multi-step, multi-enzyme cascades to be used to deliver complex multi-functional amine products and processes. The industrial partner will target the development of enzymes from the project for specific application into their new products range. Life cycle analysis and environmental impact analysis will compare the final methods with conventional chemical synthesis and allow advantages to be objectively defined.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2010.3.3-02 | Award Amount: 10.64M | Year: 2011

BIONEXGEN will develop the next generation of biocatalysts to be used for eco-efficient manufacturing processes in the chemical industry. A collaboration by industrial and academic partners have identified the key technology fields of amine synthesis, polymers from renewable resources, glycoscience and wider oxidase application as four key areas where the next generation of biocatalysts that will lead to improvements in both economic and environmental performance of the chemical manufacturing industries. This project will enable industry to use renewable resources with reduced greenhouse gas production as compared to their fossil counterparts and deliver biotechnological routes with reduced energy consumption and less toxic wastes compared to conventional chemical processes. Routes to specialised, high-value chemicals (e.g. chiral chemical compounds) normally require long chemical synthetic routes involving complex reaction steps with toxic side products and waste streams and this project will allow these methods to be replaced by clean biocatalysis routes. To broaden the range of fine and speciality chemicals and intermediates produced by biotechnological routes, research will address: (i) design and optimisation of enzymes to be used in synthetic chemistry, (ii) the selection/development of modified microorganisms which are resistant to heat, pressure or low pH when used in the production of chemical entities and allow (iii) the integration of biotechnological steps into conventional chemical processes. The project will develop and integrate with chemical steps the biotechnological manufacturing routes for the synthesis of fine and speciality chemicals especially amines, oligosaccharides and renewable polymer intermediates which are better in terms of eco-efficiency, economic potential, complexity and /or specificity of the synthetic pathways than those currently employed. Dissemination strategy will enhance the impact of this work through three separate initiatives. Economic viability and eco-efficiency will be evaluated and assessed on a quantitative basis and these results will be published in the scientific literature. Green chemistry initiatives in the BIONEXGEN project and the FP7 contributions will be presented to the wider public on a project website and through material displays at the museum in Manchester and the Big Saturday event in Manchester Science Week. An overall end of project meeting in Brussels will invite a range of political decision makers and industry leaders to attend and will ensure maximum impact. The project was devised with a strong involvement of industrial partners, in particular SMEs and is strength of this project and will contribute significantly to ensure application of the technology. This combination of technical will lead to the development of new green chemical manufacturing technology platforms that will be tested for specific targets in the European chemical manufacturing industries and use these as case studies for dissemination on a broad front.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2013.3.3-04 | Award Amount: 11.20M | Year: 2013

The INDOX proposal on industrial oxidoreductases aims to provide relevant industrial case stories to demonstrate the efficacy of optimized biocatalysts on targeted reactions, and to establish the processes scalability, sustainability and cost-efficiency versus chemical conversion processes. The chemical industry (specialties excluded) is not yet embracing enzymatic oxidation reactions to a significant extent primarily due to lack of biocatalysts with the required selectivity, availability and compatibility with the rigorous process conditions. Selected industrial oxidation and oxyfunctionalization target reactions form the basis for the INDOX screening and optimization of new biocatalysts, including: i) Intermediates for agrochemicals/APIs; ii) Polymer precursors and functionalized polymers; and iii) Intermediates for dye-stuffs. The project flow comprises: i) Recovery of selective biocatalysts from the groups of heme-peroxidases/peroxygenases, flavo-oxidases and copper-oxidoreductases from fungal genomes and other sources; ii) Improvement of their oxidative activity and stability by protein engineering (using rational design, directed evolution and hybrid approaches combined with computational calculations) to fulfill the operational and catalytic conditions required by the chemical industry; and iii) Optimization of reaction conditions and reactor configurations (including immobilization technologies and new enzymatic cascade reactions). Finally the cost efficiency compared to chemical processing will be evaluated. The INDOX approach is supported by a highly-specialized consortium of SMEs, large companies and research/academic institutions. Production of the new optimized biocatalysts and their introduction into the chemical market will take advantage from the participation of the world-leading company in the sector of industrial enzymes, together with several chemical companies willing to implement the new medium- and large-scale biotransformation processes.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2013.3.3-04 | Award Amount: 9.11M | Year: 2013

OPTIBIOCAT is a 48 months project aimed at developing biocatalysts based on feruloyl esterases (FAEs) and glucuronoyl esterases (GEs) for production of phenolic fatty- and sugar- esters with antioxidant activity for cosmetic industry, expanding the number/type of industrial biotransformations. Selected FAEs and GEs available within the consortium will be improved for their thermo- and solvent- resistance and substrate specificity by site-directed mutagenesis and directed evolution. Novel enzymes will be discovered by mining for new genes from available genomes. An inventory of novel FAEs and GEs will be developed including 50 fungal and 500 bacterial esterases, 25 site-directed and 20 directed evolved mutants. Enzymatic performances will be optimized to enhance the yield (up to the theoretical yield of 100%) and productivity (up to 0.5-1 g/l/h) of reactions giving the main targeted antioxidants: butyl ferulate, p-coumarate, caffeate, sinapate and 5-O-(trans-feruloyl)-arabinofuranose (using FAEs), glucuronate and benzyl glucuronate (using GEs). FAEs and GEs will be also tested for production of other compounds with improved biological activity and properties of hydrophilicity/hydrophobicity for cosmetic applications. Cost-effective methods will be developed for production of the new biocatalysts, in the g/L scale, and for their technical application to produce antioxidants for cosmetic industry, up to 20L. Enzyme immobilization will increase their recyclability up to ten cycles. The ability of the developed catalysts to work in conditions miming the industrial ones with reduced use of solvents and lower temperature than the chemical routes will be demonstrated. The techno-economic viability and environmental friendliness will be assessed considering a full industrial scale scenario. OPTIBIOCAT involves a highly skilled and multidisciplinary partnership of 16 partners from 8 EU countries, and it is a strongly industry driven project through the participation of 8 SMEs and 1 large company.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2011.3.4-02 | Award Amount: 13.25M | Year: 2012

BioConSepT aims to demonstrate the technically feasibility of White Biotech processes for the conversion of 2nd generation biomass into platform chemicals, which are 30% cheaper and 30% more sustainable than existing chemical routes or 1st generation processes. BioConSepT uses lignocellulose and non-edible oils & fats as cheap, abundantly available feedstocks, which cannot be used as food. The main achievements expected for BioConSepT are: (1) to develop the robust enzymes and micro-organisms suited for the more dirty 2nd generation feedstocks; (2) to reduce equipment costs and the number of process steps by the integration of bioconversion and highly selective separation technologies; (3) to facilitate easy integration in existing production chains by deploying combinations of bio- and chemical conversions and by proving the suitability of the produced platform chemicals for bio-based polymers, resins, plasticizers, solvents and surfactants and (4) by realisation of the 1st demonstration of integrated production chains from 2nd generation feedstocks to platform chemicals at industrially relevant scale. BioConSepT will bring novel technologies from lab to pilot scale by high level applied research. The consortium consists of 15 SMEs (suppliers of equipment, bioconversions, separation technologies and services), 10 large industrial parties (producers, end-users, engineering and consultancy companies) and 5 leading RTOs from 11 different countries. The large industrial parties and SMEs expect new products, processes, services and customers with a potential value of hundreds of M. BioConSepT will reduce the total processing costs and thus improve the competitiveness of the European agro/food and chemical industries. The use of renewable biomass will lead to a significant reduction of Green House Gas emissions and a more secure supply of feedstocks, energy and water as well as reduction of waste generation.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2011.3.3-02 | Award Amount: 7.77M | Year: 2011

The objective of KYROBIO project is to broaden the toolbox of single enantiomer chiral chemicals that are produced by industry in Europe using biotechnological routes. The main target is applications of lyase enzymes to selectively synthesize molecules with multiple chiral centres applying enzymatic carbon-carbon and carbon-nitrogen bond formation as the key technical platforms. We will then apply synthetic biology to improve fermentation processes in order to generate better enzymes. Chiral compounds are an important class of chemicals that biocatalytic transformation has already demonstrated great potential to compete with chemocatalysts in their production with associated benefits that come from reductions in use of organic solvents, toxic metals and energy but application has been relatively limited. KYROBIO will address the main challenges with moving forward to the next generation of added value industrial applications of white biotechnology for high value chemical synthesis. Using a supradisciplinary approach ranging from enzyme development, chemistry, molecular biology, fermentation and innovative isolation techniques the bottlenecks to applying this new technology will be overcome. It is expected that promising candidate chemicals will be commercialised within three years of completion and so scale up with economic and feasibility studies that are also key technology developments. The consortium includes a strong presence of SMEs including SME leadership and also a large multinational company which ensures multiple routes to market for the outcomes of this project. We will also have economic and life cycle analysis coupled with significant dissemination plans to ensure wider understanding of this technology that will lead to increased acceptance and uptake. The use of this environmentally beneficial technology will help to keep the European chemicals industry at the forefront of white biotechnology and increase opportunities in economic and employment.


Grant
Agency: European Commission | Branch: H2020 | Program: BBI-RIA | Phase: BBI.R10-2015 | Award Amount: 3.77M | Year: 2016

The BIOrescue project aims to develop and demonstrate a new innovative biorefinery concept based on the cascading use of spent mushroom substrate (SMS) supplemented by wheat straw (and other seasonal underutilised lignocellulosic feedstocks. i.e pruning residues, residual citrus peels and wastes). This new concept will avoid disposal and allow for the production of some biodegradable bio-based products and bioactive compounds that will help to replace the existing ones based on fossil resources. The research will help to expand the business opportunities of the mushroom cultivation farms, and the know-how and business opportunities of all the partners involved. The main innovations are: - Improved methods for the lab-based rapid (NIR) analysis of biomass - Innovative two step fractionation of SMS - Synergic effects for complete SMS glucan hydrolysis - Innovative enzyme immobilisation strategy - Development of highly efficient glucan-enzymes - Novel lignin based nano- and micro-carriers - Biopesticide production from monomeric sugars SMS derived and their packaging into nanocarriers The consortium involved is a representation of some BIC members including a large company (Monaghan Mushrooms) which is leading the proposal and some SMEs (MetGen Oy and CLEA Technologies) and BIC associate members (University of Naples and CENER). Additionally other relevant partners with well-known expertise in their respective areas contribute to the objectives. Among them some research organisations (Imperial College of London and Max Planck Institute of Polymers) and Innovative SMEs (Celignis Limited, Zabala Innovation Consulting, Greenovate Europe and C-TECH Innovation Ltd). The synergies between large industry and SMEs go beyond the scope of this project. There is a lot of potential for collaboration between agricultural industry (Monaghan) and biotechnology (MetGen and CLEA) to provide novel solutions for continuous circular economy in large agriculture-based value-chains.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2013.3.3-04 | Award Amount: 7.41M | Year: 2013

Currently the aerobic bio-catalytic oxidation reaction is the one that would have the biggest impact on the future uptake of industrial biotechnology in Europe. Chemical oxidation is both hazardous and has high environment impacts. Many oxidative bio-catalytic reactions and transformations have been identified in academic laboratories but only a very small number have been applied by industry to oxidize non-natural substrates. Hence biocatalysis for oxidative chemical manufacture processes can deliver a major advantage to the European chemical-using industries and the environment. In this project we intend to develop the tools for implementation of bio-oxidation to synthesize and oxidize alcohols. Cytochrome P450 enzymes will be investigated for hydroxylation of fatty acid derivatives and terpenes which have potential to be used in biopolymers and fragrance chemicals respectively form one line of investigation. The second is the selective oxidation of primary alcohols to give products with added value in their own right and as intermediates towards other valuable products. To support the implementation culture collections and literature reported DNA sequences will be used to identify diverse enzymes with predicted oxidase activities, which will be used as starting point for an enzyme improvement program. Then fermentation and enzyme formulation techniques will improve reaction performance to a level where useful quantities of target products can be produced for evaluation by industrial partners, and engineering techniques will analyse and implement reactor configurations that will further improve this technology platform to enable this technology to be introduced as a routine technology in the IB industry and support the European KBBE. Further a dynamic public engagement and dissemination program will be used to promote the project, IB and the FP7 program within the science community and the public, especially schoolchildren, to create extra value for the funders.


Grant
Agency: European Commission | Branch: H2020 | Program: BBI-RIA | Phase: BBI.R10-2015 | Award Amount: 5.00M | Year: 2016

Sustainable production of chemical building blocks and other added value products from plant biomass is required for a bio-based economy. However, the biomass biorefineries should benefit not only from the use of renewable feedstocks but also from greener and more efficient bio-chemical technologies. Previous projects have shown the potential of oxidative enzymes in the production of some added value compounds from biomass components. Of special interest are still unexplored oxidation/oxyfunctionalization reactions (of sugar and lipid compounds) by microbial oxidoreductases, including new (self-sufficient) heme-thiolate peroxygenases. In this context, EnzOx2 plans to develop a 100% biochemical conversion of bio-based 5-hydroxymethylfurfural (HMF) into diformylfuran, a platform chemical, and 2,5-furandicarboxylic acid (FDCA), a plastic building-block. Oxidases (flavo and copper/radical) and peroxygenases will be used to perform the three-step oxidation of HMF to FDCA in a co-substrate and side-product free, one-pot conversion. On the other hand, highly (regio/stereo) selective hydroxylation of plant lipids (such as fatty acids, terpenes and steroids) by peroxygenases will be optimized for cost-effective production of flavours and fragrances (F&F), active pharmaceutical ingredients (APIs) and others. ENZOX2 aims to solve some main bottlenecks in these industrial processes by the use of bio-chemical tools (new/engineered enzymes and optimized biotransformations), to be later validated at the pilot/flagship scale. To attain this objective the consortium includes: i) two world leaders in industrial enzymes (Novozymes) and F&F (Firmenich); ii) two chemical SMEs producing HMF and chiral APIs (AVA-Biochem and Chiracon); iii) two specialized biotechnology SMEs (JenaBios and CLEA); iv) one technology centre in the Plastics sector (AIMPLAS); and v) three CSIC institutes and two universities (Dresden and Delft) with expertise in enzyme reactions and bioprocess implementation.


Patent
Clea Technologies B.V. | Date: 2011-07-12

A non-leachable, crosslinked, on a nanometer scale formed magnetic enzyme aggregate, consisting of a non-layered, hybrid nano-composite of functionalised magnetic nanoparticles and aggregated enzyme particles, is described. The magnetic enzyme aggregate can have a high enzyme content, of up to 99%. The high enzyme content allows the use on a small scale, such as for example in a fluidised bed, of the magnetic enzyme aggregate. Also, a process for the preparation of the present magnetic enzyme aggregate is described.

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