17-ERACoBioTech: MicroalgaE as Renewable Innovative green cell facTories

17-ERACoBioTech：微藻作为可再生创新绿色细胞工厂

• 批准号: BB/R021694/1
• 负责人: Alison Smith
• 金额: $ 47.61万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR021694%2F1
• 关键词: 17; ERACoBioTech; MicroalgaE; Renewable; Innovative

This project [MERIT] sets out to leverage state of the art techniques to develop microalgae for the sustainable production of high-value, medically and industrially relevant molecules from carbon dioxide and light. Specifically, MERIT will focus on the production of twenty carbon containing (C20) molecules, known as diterpenoids. These are complex metabolites found largely in plants, and whose variety and complexity have made them incredibly interesting for numerous applications such as medicines, antimicrobial agents, and high-value chemicals. The complex structures of diterpenoids are difficult and costly to synthesize chemically and can be expensive or inefficient to purify from their native host organisms.All organisms produce the same 5-carbon building blocks used in diterpenoid production pathways. By introducing these production pathways between species, we can produce non-native diterpenoids in engineered hosts (e.g. bacteria, yeast or microalgae). Production of diterpenoid products in fermentative hosts (e.g. yeast) has become a mature technology, however, relies on unsustainable use of organic carbon sources such as glucose and inherently competes for agricultural resources. Microalgae, however, are naturally optimized to produce precursor molecules needed to make diterpenoids, as these same molecules are used for harvesting light and for generation of antioxidant pigments in the cell. Algae hold the additional benefit of rapid growth rates in simple mineral salt solutions using only light and CO2 as energy inputs. These organisms are ideal hosts for the production of diterpenes and are inherently sustainable production chassis.By introducing different enzymes that convert precursor molecules into the numerous carbon skeletons of diterpenoid products algal cells can be engineered to serve as diterpenoid production hosts. Additional engineering of these algal cells through introduction of enzymes that add oxygen molecules into the diterpene backbones will allow the algae to produce specialized diterpene structures, which often have medicinal properties. To date, engineering of microalgae to accumulate new non-native enzymes has been a major limiting factor to their widespread application as green-cell factories for complex biotechnological targets. Combining strain domestication with synthetic biology (an emerging discipline that uses engineering principles to design and assemble biological components) has recently been demonstrated to facilitate advanced engineering of these highly promising organisms. In this project, an international team representing global leaders in algal synthetic biology, outdoor algal cultivation, photobioreactor design, and process modelling, will join forces to drive forward the development of algal cell factories. The MERIT team already successfully engineered pathways for the production of several diterpenoids in microalgae. Multiple levels of strain engineering and synthetic biology will be implemented to create green-cell factories with enhanced carbon flow from CO2 to diterpenoids. Various enzymes will be combined to produce novel 'new-to-nature' diterpenoid products with potential for numerous applications. Optimized strains will be grown to scale and processes for extraction of the products will be designed. The project will generate many new avenues of commercialization potential and significantly contribute to the development of the European Bioeconomy.

该项目[MERIT]旨在利用最先进的技术开发微藻，用于从二氧化碳和光中可持续地生产高价值的医学和工业相关分子。具体来说，MERIT将专注于生产二十个含碳（C20）分子，称为二萜类化合物。这些复杂的代谢物主要存在于植物中，其多样性和复杂性使它们在许多应用中非常有趣，如药物，抗菌剂和高价值化学品。二萜类化合物的复杂结构难以化学合成且成本高，并且从其天然宿主生物体中纯化可能是昂贵的或低效的。通过在物种之间引入这些生产途径，我们可以在工程宿主（例如细菌，酵母或微藻）中生产非天然二萜类化合物。在发酵宿主（例如酵母）中生产二萜类化合物产物已经成为一种成熟的技术，然而，依赖于不可持续地使用有机碳源如葡萄糖，并且固有地竞争农业资源。然而，微藻天然地优化以产生制造二萜类化合物所需的前体分子，因为这些相同的分子用于捕获光和在细胞中产生抗氧化色素。藻类在仅使用光和CO2作为能量输入的简单矿物盐溶液中具有快速生长速率的额外益处。这些生物体是生产二萜类化合物的理想宿主，并且是固有的可持续生产底盘。通过引入将前体分子转化为二萜类化合物产物的众多碳骨架的不同酶，藻类细胞可以被改造成用作二萜类化合物生产宿主。通过引入将氧分子添加到二萜骨架中的酶对这些藻类细胞进行额外的工程改造，将允许藻类产生专门的二萜结构，其通常具有药用特性。迄今为止，微藻积累新的非天然酶的工程已经成为其作为复杂生物技术目标的绿色细胞工厂的广泛应用的主要限制因素。将菌株驯化与合成生物学（一种使用工程原理设计和组装生物组件的新兴学科）相结合，最近已被证明可以促进这些非常有前途的生物体的先进工程。在这个项目中，一个代表藻类合成生物学、户外藻类培养、光生物反应器设计和过程建模领域全球领导者的国际团队将联手推动藻类细胞工厂的发展。MERIT团队已经成功地设计了在微藻中生产几种二萜类化合物的途径。将实施多层次的菌株工程和合成生物学，以创建绿色细胞工厂，增强从二氧化碳到二萜类化合物的碳流。各种酶将被组合以产生具有许多应用潜力的新型“新自然”二萜类化合物产品。优化的菌株将按规模生长，并设计产品提取工艺。该项目将产生许多商业化潜力的新途径，并为欧洲生物经济的发展做出重大贡献。

项目成果

Exploring the impact of terminators on transgene expression in Chlamydomonas reinhardtii with a synthetic biology approach

用合成生物学方法探索终止子对莱茵衣藻转基因表达的影响

• DOI: 10.1101/2021.08.04.455025
• 发表时间: 2021
• 作者: Geisler K

The Algal Chloroplast as a Testbed for Synthetic Biology Designs Aimed at Radically Rewiring Plant Metabolism.

• DOI: 10.3389/fpls.2021.708370
• 发表时间: 2021
• 期刊: Frontiers in plant science
• 影响因子: 5.6
• 作者: Jackson HO;Taunt HN;Mordaka PM;Smith AG;Purton S
• 通讯作者: Purton S

Exploring the Impact of Terminators on Transgene Expression in Chlamydomonas reinhardtii with a Synthetic Biology Approach.

• DOI: 10.3390/life11090964
• 发表时间: 2021-09-14
• 期刊: Life (Basel, Switzerland)
• 作者: Geisler K;Scaife MA;Mordaka PM;Holzer A;Tomsett EV;Mehrshahi P;Mendoza Ochoa GI;Smith AG
• 通讯作者: Smith AG

Thiamine metabolism genes in diatoms are not regulated by thiamine despite the presence of predicted riboswitches.

• DOI: 10.1111/nph.18296
• 发表时间: 2022-09
• 期刊: NEW PHYTOLOGIST
• 影响因子: 9.4
• 作者: Llavero-Pasquina, Marcel;Geisler, Katrin;Holzer, Andre;Mehrshahi, Payam;Mendoza-Ochoa, Gonzalo, I;Newsad, Shelby A.;Davey, Matthew P.;Smith, Alison G.
• 通讯作者: Smith, Alison G.

Genetic transformation of the dinoflagellate chloroplast.

甲藻叶绿体的遗传转化。

• DOI: 10.17863/cam.41733
• 发表时间: 2019
• 作者: Nimmo I