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[优点]着手利用艺术技术来开发微藻，以可持续生产高价值，医学和工业与二氧化碳和光线的相关分子。具体而言，优点将集中于含有二十个含有（C20）分子的（称为二萜）的生产。这些是复杂的代谢产物，主要是在植物中发现的，其多样性和复杂性使它们在诸如药物，抗菌剂和高价值化学物质等众多应用中变得非常有趣。二萜的复杂结构很难化学合成，并且从其天然宿主生物体中纯化可能是昂贵或效率低下的。所有生物都会产生与二萜生产途径中使用的相同的5-碳构建块。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，酵母或微藻类）中产生非母二萜。然而，发酵宿主（例如酵母）中的二萜产品已成为一种成熟的技术，但是，依赖于使用有机碳源（例如葡萄糖）的不可持续性，并固有地争夺农业资源。然而，自然优化了微藻以产生产生二萜需要的前体分子，因为这些相同的分子用于收集光和细胞中的抗氧化色素。藻类仅使用光和CO2作为能量输入，在简单的矿物质盐溶液中具有快速增长率的额外好处。这些生物是二萜生产的理想宿主，并且是固有的可持续生产底盘。通过引入不同的酶，可以将前体分子转换为二萜类产物的众多碳骨架藻类细胞的碳骨架，以用作二萜生产宿主。这些藻类细胞的其他工程通过引入酶，这些酶将氧分子添加到二萜烯型骨架中，将使藻类能够产生专门的二萜结构，这些二萜结构通常具有药用特性。迄今为止，微藻的工程以积累新的非本地酶是其广泛应用的主要限制因素，作为复杂生物技术目标的绿色工厂。最近已证明将应变驯化与合成生物学（一种使用工程原理设计和组装生物学成分的新兴学科）相结合，以促进这些高度有希望的生物的先进工程。在这个项目中，代表藻类合成生物学，室外藻类种植，光生反应器设计和过程建模的全球领导者的国际团队将联手推动藻类细胞工厂的发展。功绩团队已经成功地为在微藻中生产了几种二萜类化的途径。将实施多个级别的应变工程和合成生物学，以创建从CO2到二萜的增强的绿色工厂。各种酶将被合并，以生产具有许多应用潜力的新型“新的”二萜类产品。将设计优化的菌株扩展，并设计用于提取产品的过程。该项目将产生许多新的商业化潜力途径，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

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

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

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

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.