Synthetically engineered microalgae for improved gut function and human health

微藻是一种小型微型植物，能够产生重要的营养成分，包括蛋白质、碳水化合物和脂肪。它们甚至可以用来隔离二氧化碳，并制造有用的产品，如营养食品、药品、生物材料和生物燃料。它们通常生长在水中，可以吸收营养物质，提供更清洁的废水，减少富营养化。自20世纪70年代以来，将微藻的这一愿景变为现实一直是许多科学家和工程师关注的焦点。它们已被宣布为世界问题的解决方案，能够在世界人口到2050年增长到90亿时解决营养短缺问题，在世界遭受气候变化时减少二氧化碳排放，并在世界减少对化石燃料和材料副产品的依赖时产生可持续的经济。然而，为了实现这一愿景，从实验室扩大到商业上有用的过程存在一些障碍。主要的瓶颈是大规模种植藻类的能力，利用廉价的营养物质，以及脱水过程，即从水中提取藻类(脱水)，然后从微藻中提取有用的化合物。格拉斯哥大学的实验证明，在薄膜上种植微藻是一种克服脱水成本的方法，在经济和能源方面都是如此。以这种方式生长它们，使它们能够作为生物膜生长。在这种情况下，很少有人研究这种生物膜的形成，但从这项工作中可以清楚地看出，有时产量很低。拥有可靠和高产量并了解生长条件(例如底物材料、温度、pH、水分活度)的影响对于推进和扩大应用非常重要)。最近，世界在操纵不同生物的基因组方面发生了令人难以置信的变化，许多这方面的工作都集中在细菌上，但人们对能够操纵微藻来改善其特征的兴趣越来越大，例如生长速度或过度表达某些分子化合物。工程微藻作为生物膜生长的工作还很少，这是当前项目的重点。薄膜光生物反应器将用复杂而简单的控制系统来监控生物膜的生长，并使用从食品级废物流中提取的营养物质。它们的性能将用野生型微藻菌株进行评估，然后将用工程微藻观察提高微藻产量和特性的能力。具体地说，作为开发和展示这些新方法的一种方式，将过度表达的成分将包括维生素B12，这是一种人体无法产生的基本维生素，叶黄素(一种胡萝卜素，在人眼的黄斑和视网膜中发现)和胞外多糖(EPS，有助于肠道健康)。一旦培养完成，样品将在“组学”的保护伞下，使用最先进的设备进行分析和比较，从而能够对蛋白质、碳水化合物和脂肪进行详细评估。还将使用体外模型评估样本对肠道功能的影响。将开发控制系统，并从过程的每个部分收集数据，以开发新的模型、评估生命周期分析、技术经济评估和新的机器学习代码，以帮助理解这项工作的机会。最终，这项工作将作为一个新的研究领域的基础，通过改善营养发展来影响社会，并跳板到其他领域，影响可持续性和气候变化。

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.