Algal oils by design: a new biotech platform for high-value lipids.

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Industrial biotechnology (IB) is the harnessing of biological processes and materials for the production of industrially useful products on a large scale. If offers novel solutions to product synthesis that avoid fossil fuels, but instead use plants, bacteria, fungi and algae as renewable sources. This bio-economy is currently worth trillions globally and new advances could bring major benefits to UK industry sectors including chemicals, renewable energy, materials, and health, and could create thousands of jobs in the coming years. A major area of IB is the intensive cultivation of specific microorganisms in industrial scale fermentors, where the microbes have been selected or engineered to produce high levels of a desired commercial product such as an antibiotic, a complex metabolite or a therapeutic protein. These fermentation processes generally use either bacterial or fungal species as the 'cell factory'. However, a very large and diverse group of microorganisms - the algae - represent a rich biological resource that has yet to be exploited in the biotech industry. These photosynthetic microorganisms not only offer a huge treasure trove of natural compounds that have potential application in drug discovery (e.g. as nutraceuticals and food additives, as natural colorants or stabilizers in food and cosmetics) but also offer the possibility of cultivation using sunlight and CO2 to drive biological production, rather than the expensive sugars needed for bacterial or fungal growth.In this proposal we aim to develop algae as cell platforms for IB applications, and in doing so bring a new, disruptive technology to the fore. We will build on recent advances in our knowledge of the genetics, biochemistry and physiology of algae, together with developments in genetic engineering and high-throughput cell screening technologies. As a focus for this four year project we will develop the algal platform initially for the production of high value oils (=lipids) such as the edible omega-3 and omega-6 long-chain fatty acids that are an essential component of animal diets, and contribute, inter alia, to infant brain development and cognitive function in adults.The multidisciplinary project has four integrated programmes of work and builds on the world-leading expertise of the five participating groups. We will combine our biological knowledge on the genomes, transcriptomes and lipid metabolomes of two chosen algal species with advanced metabolic modeling tools to build a detailed, robust and predictive model of lipid metabolism in the algal cell. Such as model will allow us to evaluate in silico the effects of manipulating the lipid biology (for example by adding new enzyme pathways). In a second programme, we will use our expertise in algal genetic engineering to develop synthetic biology tools and a design pipeline that will greatly accelerate the process of creating genetic engineered strains. This is critical since, even with a sophisticated model, a large number of different engineering parameters need to be evaluated in order to achieve a fully optimized strain. Such strain selection will also be facilitated by integrating the genetic engineering with a high-throughput cell evaluation technology developed by one of the groups. This system involves encapsulation of single cells in oil microdroplets and ultra-fast analysis and sorting using microfluidic technology coupled to analytical equipment. This will enable the rapid identification and recovery within large populations, of rare engineered or mutated cells that have the desired phenotype. Finally, the technologies will be brought together and tested in the final programme to confirm that we can design and create 'bespoke' strains producing high levels of a desired oil.