Synthetically engineered microalgae for improved gut function and human health

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

Microalgae are small microscope plants that have the ability to produce important nutritional components, including proteins, carbohydrates and lipids. They can even be used to sequester carbon dioxide and make useful products such as nutraceuticals, pharmaceuticals, biomaterials and biofuel. They usually are grown in water and can absorb nutrients providing cleaner waste water and reduce eutrophication. Making this vision for microalgae a reality has been the focus of many scientists and engineers since the 1970s. They have been declared a solution to the world's problems, being able to address nutrition shortages as the world's population grows to 9 billion people by 2050, reduce CO2 emissions as the world suffers from climate change and produce a sustainable economy as the world reduces its reliance on fossil fuels and the material by-products.
To achieve this vision, however, there are hurdles associated with the scaling-up process from laboratory to what would be considered useful commercially. The main bottlenecks are on the ability to grow algae at scale, utilising inexpensive nutrients, and the dewatering process, or extracting the algae from the water (dewatering), and then extraction of useful compounds from the microalgae.
Experiments at the University of Glasgow demonstrated growing microalgae on thin films as a way to overcome dewatering costs, financially and in terms of energy. Growing them in this way, allows them to grow as a biofilm. Little work has been done investigating this biofilm formation in this context but it was clear from this work that the yields were low on occasions. Having a reliable and high yield and understanding the impact of growth conditions (e.g. substrate material, temperature, pH, water activity) is important to progress and scale the applications).
Recently, the world has seen incredible changes in being able to manipulate genomes of different organisms, a lot of this work has focussed on bacteria, but there is a growing interest in being able to manipulate microalgae to improve their characteristics e.g. growth rate or overexpress certain molecular compounds. Little work has been done on engineering microalgae to grow as biofilms, which is the focus of the current project. Thin film photo bioreactors will be built with sophisticated, yet simple, control systems to monitor biofilm growth, and use nutrients extracted from food-grade waste-streams. Their performance will be assessed with wild-type strains of microalgae, and then the ability to improve the microalgae yields and characteristics will be observed with engineered microalgae. Specifically, components that will be overexpressed as a way of developing and demonstrating these new methodologies will include Vitamin B12, which is an essential vitamin that cannot be produced in the body, Lutein (a carotenoid, found in the human eye in the macular and retina) and exopolysaccharides (EPS, which can help gut health). Once grown, samples will be analysed and compared using state of the art equipment, under the "omics" umbrella, allowing detailed assessment of proteins, carbohydrates and lipids. Samples will also be assessed for their impact on gut function using in-vitro models.
Control systems will be developed and the data collected from each part of the process to develop new models, assessing life cycle analysis, techno-economic assessment and new machine learning codes to help understand the opportunities from this work.
Ultimately the work will serve as the bases for a new area of research to impact society through improved nutrition development, and spring board into other areas to impact sustainability and climate change.

Technical Summary

Strains of Chlamydomonas reinhardtii and Synechocystis sp PCC 6803 will be engineered to improve their potential to grow as a biofilm. Alongside these modifications, certain genes will be promoted or knocked out to provide model organisms that will over produce vitamin B12, Lutein, exopolysaccharide and extracellular sulphate-polysccharide. This offers opportunities to exploit novel thin film photobioreactors (TFPBRs) that support their growth, and allow a drastic reduction in dewatering costs, (one of the main hurdles inhibiting large-scale deployment and commercialisation of microalgal biorefineries). Another hurdle, nutrient cost, is overcome by utilising food-grade waste-streams to support microalgal growth; potato waste streams have been selected because of their UK availability and proven impact on supporting growth.
The study is centred around the benefits of these new approaches to microalgae production to enhance human gut function and nutrition. The wild-type and engineered organisms will be grown in PBRs and TFPBRs, and growth compared under different abiotic conditions, assessing yields and nutrient-mismatch behaviour.
Performance metrics will include yield and production of the overexpressed components. Alongside growth trials, data will be captured to allow development of real-time sensors and systems to monitor performance, through analysing spectral data (e.g. Raman, IR spectra, fluorescence) and correlation with omics, improving control systems and optimal harvest times.
Grown algal samples will be used raw and with simple low temperature, and/or solvent extraction systems and used in gut function models to identify benefits to human health. Samples will be analysed using omics to further elucidate on the gut function models and benefits of the engineered algae.
Simple LCA and TEA models will be developed to quantify benefits from these approaches and identify roadmaps to commercialisation and new areas of productive research.

Publications

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