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

设计藻油：高价值脂质的新生物技术平台。

• 批准号: BB/L002957/1
• 负责人: Saul Purton
• 金额: $ 301.21万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL002957%2F1
• 关键词: Algal; oils; design; new; biotech

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.

工业生物技术（IB）是利用生物过程和材料大规模生产工业用产品。 If 提供了新颖的产品合成解决方案，避免使用化石燃料，而是使用植物、细菌、真菌和藻类作为可再生资源。这种生物经济目前在全球价值数万亿美元，新的进步可能会给英国工业部门带来重大利益，包括化学品、可再生能源、材料和健康，并可能在未来几年创造数千个就业机会。 IB 的一个主要领域是在工业规模发酵罐中对特定微生物进行强化培养，其中微生物经过选择或改造以生产高水平的所需商业产品，例如抗生素、复杂代谢物或治疗性蛋白质。这些发酵过程通常使用细菌或真菌物种作为“细胞工厂”。然而，一个非常庞大且多样化的微生物群体——藻类——代表了生物技术行业尚未开发的丰富生物资源。这些光合微生物不仅提供了天然化合物的巨大宝库，这些化合物在药物发现方面具有潜在的应用（例如作为营养保健品和食品添加剂，作为食品和化妆品中的天然着色剂或稳定剂），而且还提供了利用阳光和二氧化碳进行培养的可能性。驱动生物生产，而不是细菌或真菌生长所需的昂贵糖。在这项提案中，我们的目标是开发藻类作为 IB 应用的细胞平台，并在此过程中为 IB 应用带来一种新的、颠覆性的技术。前面。我们将利用藻类遗传学、生物化学和生理学知识的最新进展，以及基因工程和高通量细胞筛选技术的发展。作为这个为期四年的项目的重点，我们将开发藻类平台，最初用于生产高价值油（=脂质），例如可食用的 omega-3 和 omega-6 长链脂肪酸，它们是动物饮食的重要组成部分，并为婴儿大脑发育和成人认知功能做出贡献。该多学科项目有四个综合工作计划，并以五个参与小组世界领先的专业知识为基础。我们将把我们对两种选定藻类的基因组、转录组和脂质代谢组的生物学知识与先进的代谢建模工具结合起来，建立一个详细、稳健和预测的藻类细胞脂质代谢模型。这样的模型将使我们能够在计算机上评估操纵脂质生物学的效果（例如通过添加新的酶途径）。在第二个项目中，我们将利用我们在藻类基因工程方面的专业知识来开发合成生物学工具和设计管道，这将大大加快创建基因工程菌株的过程。这一点至关重要，因为即使使用复杂的模型，也需要评估大量不同的工程参数才能实现完全优化的应变。通过将基因工程与其中一个小组开发的高通量细胞评估技术相结合，也将促进这种菌株的选择。该系统涉及将单细胞封装在油微滴中，并使用与分析设备相结合的微流体技术进行超快速分析和分类。这将能够在大量群体中快速识别和恢复具有所需表型的稀有工程或突变细胞。最后，这些技术将在最终计划中进行整合和测试，以确认我们可以设计和创建“定制”菌株，生产高水平的所需油。

项目成果

Domestication of the green alga Chlorella sorokiniana: reduction of antenna size improves light-use efficiency in a photobioreactor.

• DOI: 10.1186/s13068-014-0157-z
• 发表时间: 2014
• 期刊: Biotechnology for biofuels
• 影响因子: 6.3
• 作者: Cazzaniga S;Dall'Osto L;Szaub J;Scibilia L;Ballottari M;Purton S;Bassi R
• 通讯作者: Bassi R

Applications of Microalgal Biotechnology for Disease Control in Aquaculture.

• DOI: 10.3390/biology7020024
• 发表时间: 2018-04-12
• 期刊: Biology
• 影响因子: 4.2
• 作者: Charoonnart P;Purton S;Saksmerprome V
• 通讯作者: Saksmerprome V

Selectable Markers and Reporter Genes for Engineering the Chloroplast of Chlamydomonas reinhardtii.

• DOI: 10.3390/biology7040046
• 发表时间: 2018-10-10
• 期刊: Biology
• 影响因子: 4.2
• 作者: Esland L;Larrea-Alvarez M;Purton S
• 通讯作者: Purton S

Triacylglyceride Production and Autophagous Responses in Chlamydomonas reinhardtii Depend on Resource Allocation and Carbon Source

• DOI: 10.1128/ec.00178-13
• 发表时间: 2014-03-01
• 期刊: EUKARYOTIC CELL
• 作者: Davey, Matthew P.;Horst, Irmtraud;Smith, Alison G.
• 通讯作者: Smith, Alison G.