17-ERACoBioTech: MicroalgaE as Renewable Innovative green cell facTories

点击翻译按钮获取中文摘要

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.