Waste-free chemical processes are pivotal for a sustainable society. In nature, large and complex protein structures have evolved to achieve extremely selective and efficient enzyme catalyzed conversions. Unfortunately, nature does not provide enzymes for the synthesis of the many pharmaceuticals, agrochemicals and fine-chemicals that are needed. Using our recently developed method (Angew. Chem. 2010, 49, 5315), we want to establish a paradigm shift in catalysis research by developing 'artificial enzymes' containing transition metals that nature has not acquired for the production of important products. In addition to the 'traditional' toolbox of ligand backbone constraints and steric and electronic ligand modification, the use of molecular recognition and secondary interactions by proteins will be exploited. Incorporation of well-designed transition metal phosphine and nitrogen complexes into proteins will lead to a new world of artificial metalloenzymes. Therefore, the aim of the proposed research is the development of artificial late transition metal based metalloenzymes for important catalytic transformations for which no enzymes are known, aspiring to selectivities and activities that rival enzymatic catalysis. The resulting artificial transition-metalloenzymes are anticipated to exhibit activities and selectivities comparable to natural enzymes, but the presence of the synthetic catalytic moiety will extend their reaction repertoire beyond the limits of natural enzymes. The catalytic performance of these hybrid catalysts can easily be optimized by using orthogonal structural-diversity generating procedures: molecular biology for the optimization of the protein structure and synthetic chemistry to tune the structure of the ligand. This so-called chemogenetic optimization strategy has already been shown to be a powerful approach in optimizing the catalytic properties of hybrid catalysts. To maximize the possibilities for functional interactions of the proteins with substrates and the phosphine-ligands, we will modify proteins naturally containing suitable binding pockets, like fatty acid binding proteins. Recently, the crystal structure of Human Peroxisomal Multifunctional Enzyme Type 2 (MFE-2) has been solved. This crystal structure revealed a large apolar molecular tunnel, containing a Triton X-100 molecule. This apolar tunnel of MFE-2 can be exploited for selective uptake of apolar substrates and correct positioning of the metal center can result in selective exposure of the center of reactivity of the substrate to the catalytic site, like in natural enzymes. Encapsulating substrates by these 'synthetic proteins' will ultimately enable clean conversion of apolar unfunctionalised alkenes as for instance in selective rhodium catalyzed hydroformylation of alkenes, a reaction for which no natural enzymes are known. We have recently developed a robust and reliable method to couple a wide variety of phosphines to virtually any protein via a single reactive cysteine residue. Preliminary results showed that a phosphine modified Human Peroxisomal Multifunctional Enzyme Type 2 (MFE-2) gave two orders of magnitude rate acceleration in the the aqueous rhodium catalyzed hydroformylation of long chain alkenes. We now want to explore the full potential of these hybrid homogeneous and biocatalysts in biotechnological applications. We propose to use MFE-2 and other proteins as templates for shape-selective rhodium catalyzed hydroformylation of long chained terminal and internal alkenes, a demanding transformation using existing technologies. Functionalization of their binding sites at different positions with various phosphine ligands is anticipated to result in improved selectivity for the terminal aldehydes, which are extremely desirable feedstocks for the chemical industry. The concept will be extended to other important catalytic reactions like C-C couplings, C1-selective oxidation of alkanes and C-H activation.

There is an urgent need to address the accelerating increase in global CO2 emissions and atmospheric CO2 levels while providing fuels to meet growing energy needs. The UK government has targeted an 80% reduction in emissions (from 1990 levels) by 2050 with an interim target of 34% reduction by 2020. Increasingly, it is becoming clear that a key approach to storage of variable sustainable energy sources such as solar or wind power is in the form of stored chemical energy, and that this is likely to be as a form of hydrogen. However, although hydrogen itself has excellent enthalpy content per unit weight, it is a low density gas, has storage difficulties, and requires relatively high compression energy. The present proposal is focused on the conversion of sustainably produced hydrogen to high energy density liquid fuels including methanol, DME and hydrocarbons which are more easily transported and are compatible with existing fuel distribution networks. These fuels are low in sulfur and flexible in their contribution to future low carbon-intensity fuel scenarios by displacing fossil sources from the liquid fuels pool. They can be used for transport fuels (where they are likely to remain the focus for some time to come), as blending components, as seasonal storage candidates (exploiting their permanence and energy density), for distributed power production or for local heating. The synthesis of these liquid fuels will be achieved using CO2 as a vector to react with hydrogen from solar or wind inputs. We therefore aim to develop new technology to reduce the atmospheric CO2 burden by utilising only water as a source of this hydrogen, avoiding highly endothermic thermocatalytic steam reforming. The annual CO2 emissions from UK electricity generation (around 150x10^6 tonnes) is sufficient, in principle, to supply the UK requirement for liquid transportation fuels, or three times the amount required for the world annual production of methanol (around 45x10^6 tonnes). There are a number of possible attractive concentrated point sources of this CO2, including CO2 prepared for sequestration or from ammonia plants, which could be used to make liquid fuels in the medium term provided efficient catalytic technologies could be developed. Thus we will develop new catalytic technology for the production of synthesis gas (CO/H2) and simple fuel organics, ultimately driven by solar energy using CO2 and H2 sustainably produced from water. We will explore integration of hydrogen and syngas generation with production of syngas from biogenic sources such as waste or biomass to provide additional feed flexibility. Part of our work will develop novel and targeted catalysts for the thermocatalytic production of 'green' fuels from syngas with variable CO2, H2 and water content, focused by process systems engineering considerations that specifically address low-carbon aspects such as intermittency of primary renewable power in process design. Industry partners have endorsed the approach and will provide key input into the form of point source CO2 supply, catalyst manufacture, liquid fuel synthesis, electrolyser manufacture, sustainable hydrogen generation and technology integration, life cycle analysis and industrial fuel usage. The proposal adopts a multidisciplinary catalyst discovery, deployment and process engineering approach to develop, evaluate and optimise thermal, photo- and electro-catalysed routes to liquid fuels from CO2 and water using solar energy (and, indirectly, wind or marine power). Direct thermal and solar-assisted paths to methanol and DME will be compared with stepwise solar/electrochemical syngas generation plus thermal DME or Fischer-Tropsch hydrocarbon synthesis paths. The novel catalyst chemistries enabling each route will be integrated on the basis of process systems modelling and analysis to identify optimised schemes that will be benchmarked by input from industry partners with key roles in potential supply chains.

Our aim is to develop a sustainable, integrated platform for manufacture of industrial chemicals based on biological terpenoid feedstocks to complement carbohydrate, oil and lignin-based feedstocks that will be available to sustainable chemistry-using industries of the future. Our focus will include production of aromatics and amines which are particularly challenging targets from other biofeedstocks. Transition from fossil-based feedstocks to renewable alternatives is a key challenge for the 21st Century. Major efforts are underway to address this with work currently focused on carbohydrates, fats and oils, and lignins all of which give rise to fundamental technological barriers due to the incompatibility of complex and oxygen-rich materials with conversion technologies developed for simple hydrocarbon-based petrochemical feedstocks. This often requires biological feedstocks to undergo costly and inefficient transformations and separations prior to deployment in existing supply chains. In contrast, terpenes are an abundant class of natural products based on the C5 isoprene unit. As hydrocarbons they are easily separated from aqueous environments and can be readily upgraded using existing petrochemical technologies. While terpenes have been used in limited quantities since antiquity (notably as flavours and fragrances) they have yet to be exploited systematically for the production of platform chemicals even though they represent a potentially vast resource: global biogenic production of terpenes is 10^9 t/yr. Significant volumes of useful terpenes are already available on global markets at low cost (production of turpentine oils and limonene are 330,000 and 30,000 t/yr, respectively, the former costing 0.09-0.19 Euros per L). While this is sufficient in itself to justify a viable value-added chemical platform (metrics comparable to those for lignin: 1.1m t/yr at £250-2,000 per t) such figures will be dwarfed in the near future through the large-scale (multimillion t/yr) microbial production of terpenes such as farnesene for biofuels via the engineering of isoprene metabolic pathways. This industrial biotechnology (IB) approach, developed by Amyris and others, promises large-scale and geographically flexible supplies of terpenes via fermentation of plant sugars and cellulosic waste. Thus, the exploration of new generic technologies for the chemical exploitation of terpenes is timely, not only in terms of sustainable utilization of current global resources, but also to take advantage of major developments in IB. However, key challenges to be addressed in the context of terpene-based manufacturing include: (i) development and optimization of sustainable chemical transformations; (ii) scale-up of intensive conversion processes; (iii) development of new terpene sources; and (iv) systems-level understanding of technical, environmental and economic factors associated with new terpene-based manufacturing technologies. This project will address these challenges directly in four interconnected workpackages. Outputs from the project will provide a competitive advantage for one of the UK's most successful industries. Chemistry-reliant industries contributed an equivalent of 21% GDP to the UK economy in 2007, they support 6m jobs (RSC 2010), and turnover is growing at 5% pa (UKTI, 2009). The utilization of IB is vital to sustaining competitive advantage, with the value of the UK IB market in 2025 estimated at £4b to £12b (BERR 2009). Specific to this project, the development of new integrated technologies for terpene-based manufacturing, ultimately via microbial fermentation of waste cellulose, will provide competitive advantage for UK industries through new sustainable manufacturing processes, reduced feedstock costs, security of supply and reduced environmental impact. The UK will benefit further from export of new technologies and services and from development of new skills vital to future low carbon manufacturing.