Combinatorial metabolic engineering platform for the production of valuable compounds in the alga Euglena gracilis

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Sustainable development with net zero greenhouse gas emissions will require new technologies to capture CO2 and make valuable products. Photosynthetic algae can realise this goal, turning CO2 into biomass and high value compounds, such as the dye astaxanthin. Recent advances in algal metabolic engineering allows yield increase for the natural products, but also the introduction of novel genes and pathways to make desired compounds with minimal environmental impact. Euglena gracilis is an important alga due to its complex evolutionary history, genetic and cellular diversity, unique biology, and intricate metabolism, allowing it to produce a wide array of metabolites. Industrial interest in Euglena has led to it being used for the production of biofuels, due to its synthesis of wax esters, for bioremediation, due to its ability to grow In a wide range of environments and sequester heavy metals, and for the production of nutritional supplements, due to its synthesis of polyunsaturated fatty acids and B-glucans. Despite the opportunities for metabolic engineering to produce high-value biomolecules in Euglena, efficient genetic engineering tools are limited. Establishing an efficient transformation method and advanced synthetic biology toolkit for metabolic engineering of E. gracilis would increase the value of this alga for industrial biotechnological, as well as provide tools for the understanding of fundamental biology in this group of organisms. In this project the student will develop a platform for assembly and optimisation of metabolic pathways in Euglena and apply them for the production of high value molecules from atmospheric CO2. In order to control and optimise the production, a wide range of considerations are involved, from the cellular location of the proteins to their relative abundance and the impact on growth. The student will evaluate relative production levels from different control elements and develop inducible parts. They will develop parts with the ability to target proteins to the correct subcellular location, using targeting peptides or organelle transformation. Building on recent successes in other organisms, combinatorial assembly using libraries of different parts will be used at all stages to optimise production.The student will apply the tools developed in the earlier parts of the project to produce high value proteins and products in Euglena for industrial or medicinal uses. Initial targets will be single proteins, such as the human erythropoietin for pharmaceutical use, viral core proteins as scaffolds for nanotechnology and single enzymes for the synthesis of high value molecules, such as the terpene caryophyllene. More complex biosynthetic pathways will then be developed, such as the three-enzyme cascade for the biosynthesis of the antimalarial precursor artemisinic acid. The optimised production platforms will be analysed for their potential for the environmentally friendly industrial production of these high value compounds. The student will gain training in algal biotechnology, synthetic biology and metabolic engineering.