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Plant cuticle secondary metabolite network
The plant cuticle provides a unique resource for a wide range of functional molecules that have a wide range of applications from anti-transpirants to insect semiochemicals. Isolating these molecules can require a different approach to other plant metabolites and this area of plant chemistry has commercial interest, support from other academic groups and independent research organisations. We would be interested in your views on the value of this as a discrete network.
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Predicting Bioreactor Performance
Knowing likely product yield early in bioprocess development is critical to making correct, evidence-driven commercial decisions. Currently it is extremely difficult to make early, realistic predictions of how the industrial-scale bioreactor will perform. I'd like to propose a network to develop new technologies to quantitatively predict product yield within the bioreactor. This will help companies make go/no-go decisions early in bioprocess development. Key technologies will be genome-scale and statistical models, and, to inform these, bench-scale methods for bioprocess characterisation (i.e. parallel mini-bioreactors). This will require input from areas including computational systems biology, particularly GSMs; machine learning and system identification; bioreactor automation and optimisation; a whole range of bioanalytical methods; and, significantly, from companies with bench-scale methods for characterising large-scale reactors.
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Predictive and rapid enzyme/pathway engineering to underpin the IBBE agenda
Predictive/rapid design of enzymes/pathways will be key to their exploitation in emerging industrial biotechnology industries, and will therefore underpin more sustainable manufacturing processes. Predictive/rapid design will therefore impact widely in ‘synthetic biology’ and industrial biocatalysis with novel enzymes/pathways used in bulk/fine chemicals manufacture, biofuels/energy industries, food production and security. This proposed network will secure unique expertise in theory and experiment, and embrace new enabling methods (computation, robotics, experimental method development etc) to ensure that the emerging biotechnology industries are supported by relevant state-of-the-art bio-catalysis/enzyme design research and training across all disciplines that feed into enzyme engineering. The network would cut across discipline boundaries uniting the efforts of theoretical and experimental biologists, chemists, computational scientists, physicists and engineers, and contribute towards achieving more rapid engineering of stable/fit-for-purpose enzymes that can be more rapidly exploited in industrial biotransformations and synthetic biology/metabolic engineering. Our ability to rpredictively design new bio-catalysts for manufacture, or re-profile existing biocatalysts enzymes, will be enhanced if we develop more comprehensive, physical and predictive models from which to understand the origin of catalytic power and specificity. Likewise the development of smarter ways to screen/evolve enzyme variants is also required. This proposed network, with a strong enabling technologies theme, would address these key limitations with a view to accelerating enzyme discovery/design for industrial biotechnology applications.
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Process integrated microbial production of chemicals from renewables
The ability to engineer E coli and S cerevisiae for production of a variety of chemicals is now established. However, few of these examples are industrially viable due to problems with product toxicity, poor atom efficiency etc. While clearly overlapping with some existing suggestions I think it would be valuable to create a network that could address the issue of microbial "producability" in an interdisciplinary manner. This would need to be led by an industry pull where the user community helps to define a range of types of molecule (typically a synthetic precursor rather than a defined end product) that should be targetted. The range of biologically produced targets can then be extended by considering economically feasible chemical or biological transformations that could produce these precursors from compounds that could be obtained through metabolic engineering. With a panel of opportunities (and assistance from synthetic chemists) it should be possible to address issues of metabolic efficiency, toxicity, tolerance/resistance mechanisms and product recovery (and related issues of substrate purity) in an integrated manner in order to assess economic feasibility before investing time and effort into metabolic engineering. The work will require continuous evaluation of economic feasibility (including vs chemical synthesis), significant involvement from end -users and SMEs interested in rpoduction possibilities and should not be predicated on a single type of organism.
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Protein & Peptide Engineering Network
This network aims to be a multidisciplinary group focused on protein and peptide engineering with the goal of producing the next generation of polypeptides with enhanced functionality. These proteins may include therapeutic, diagnostic, functional proteins as well as those with catalytic capability. The group may include (but not be limited to) people with the following skills; structural biology, directed evolution, protein folding, peptide synthesis, protein design, protein evolution, molecular dynamic simulation, phage display, proteomics, bioinformatics, genetic engineering, biochemical engineering, formulation, biosafety, regulatory affairs and bioethics. This field is not limited to obvious therapeutic proteins such as fusion proteins and modified antibodies. It can include designer peptides and functional proteins such as anti-freeze and anti-wetting proteins.
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Understanding the full production cycle from biomass to target chemicals
Is there scope for a more holistic network which will include expertiese from other networks such as Genomics/Enzymology, Bioprocessing, Catalytic Processing/Selective Chemistry, Chemical Engineering, Modelling and Simulation, etc and which will help to identify promising routes and roadmaps for the conversion of UK relevant feedstocks to UK relevant products?
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using chemistry to diversify complex biomolecules
I think there is scope to try to combine bacterial cell based approaches to do the 'hard' complex backbone synthesis with stereocentres . Often purely chemical methods fail to generate these precursors in sufficient amount or cost effectively. However purely cell based systems are often limited in their diversity. There are several exciting examples of encoding reactive functional groups into 'natural' products that could then subsequently be used to diversify the backbone (priveldged scaffold). Not only would compound choice be increased bur favorable properties or tracers could be introduced. I think such project would of course need enzyme chemists, biochemists, microbiologists and crucially solid phase organic chemists.
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Yeast Technologies Network
We propose an industrial biotechnology network focused on yeast. Industrial biotechnology relies to a large extent on microbial cell factories, the products of which are dependent on the constituent metabolic pathways and their regulation. Yeasts provide an important platform for current and future industrial biotechnology. They are already well established for the global production of ethanol. However they are also proving to be important in the industrial production of platform and fine chemicals. Organic acids (e.g. succinic acid) and industrial surfactants (e.g. sophorolipids) are already produced commercially using yeast. The network will address two key questions. The first is whether these processes can be improved and, if so, what other high value chemicals can be made in this way? The second concerns extending the range of substrates (e.g. sources of waste biomass) that may be converted to platform chemicals. Both questions will benefit from the exploitation of yeast genetic and metabolic diversity (both within yeast and within other microbial platforms). We have strong interest in the proposed network from Croda, Diageo, Lallemand and Vireol and support from academic partners at Cambridge University (Systems Biology), Imperial College London (Synthetic Biology) and Nottingham University (Genome Dynamics). Overseas support and advice has been offered by Great Lakes Bioenergy, US Department of Energy. We propose that the network be led from the National Collection of Yeast Cultures (NCYC), a BBSRC supported National Capability which has recently initiated a project to sequence the genomes of all 4,000 yeasts in the collection. We further propose that the NCYC be supported in this role by the IFR Biorefinery Centre, itself networked to key commercial interests involved in biorefinery processing of agrifood waste and closely-linked to exciting developments in industrial biotechnology on the Norwich Research Park, one of three BBSRC Innovation Campuses.
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