SynBio4Flav - industrial production of flavonoids thanks to synthetic biology

A project from the Horizon 2020 programme financed by the European Commission, called "Synthetic microbial consortia-based platform for flavonoids production using synthetic biology", has been implemented at the Department of Chemistry since January 2019. This is the first H2020 research and innovation (RIA) project at the University of Environmental and Life Sciences in Wrocław and at the same time the largest in financial terms. Its budget is nearly 7 370,000 EUR, 528,000 of which will go to our University.

The SynBio4Flav project obtained funding under the sub-measure called 'a leading position in assistive and industrial technologies – biotechnology', hence its primary goal is to develop a competitive industrial process for obtaining flavonoids that will become an engine for innovation in many sectors of the European economy.

Flavonoids are natural products of plant origin, which are common components of our diet. They show many beneficial health effects, such as protection against chronic and degenerative diseases like cancer, cardiovascular diseases, strokes or brain and the immune system disorders. Their uses are diverse and apply to many industries. In the food sector, they are widely used as natural food colourings and flavour enhancers. They are also used in the pharmaceutical industry, nutraceuticals, animal feed and cosmetics. The industrial use of flavonoids is mainly restricted by their very availability, resulting from the relatively narrow range of suitable plant sources, frequently low content and biodiversity which hinders purification processes. As a result, large amounts of plant biomass are needed to obtain even small amounts of pure compounds. Despite growing demand, a process for the profitable production of flavonoids by chemical synthesis or biotechnological methods has not yet been developed.

The response to this challenge is the SynBio4Flav project, which offers a completely new approach to the biotechnological production of complex natural compounds such as flavonoids. The aim of the project is to implement standardized solutions for flavonoid production by consortia of optimized microbes which would be an alternative for plant sources. Instead of optimizing a single whole-cell biocatalyst, which is currently the approach most commonly used in synthetic biology, complex metabolic pathways of flavonoids present in plants will be broken down into smaller elements and transferred to various microorganisms that together will form a single consortium. Each of these microorganisms will be genetically programmed to ensure optimal performance of the respective stages of biosynthesis. It is expected that this innovative approach will result in significantly better performance and cost efficiency. SynBio4Flav will verify its technology in an industrial environment to achieve the fifth level of technological readiness (TRL5) in the production of natural and new functionalized flavonoids. A measurable result of the project will be the creation of a library of optimized and compatible cellular systems (modules) suitable for use in new synthetic biological assemblies. The modular design of the production process will allow us to achieve targeted biosynthesis of hundreds of different flavonoids with the desired biological properties.

Eleven consortium members, including six scientific units and five industrial partners, participate in the project, which will last 50 months. The project coordinator is prof. Juan Nogales from the Consejo Superior de Investigaciones Científicas in Madrid, Spain's largest public research institution.

The project involves specialists in synthetic biology, systems biology, protein engineering, biocatalysis, preclinical research on model systems, and increasing laboratory fermentation and bioprocesses to industrial scale. The team includes also SME and industrial partners who are market leaders in the field of natural products (mainly flavour and aroma-adding ones) and a company with extensive PR experience.

The project is carried out by the team of professor Ewa Huszcza, consisting of Tomasz Tronina BEng, PhD, Jarosław Popłoński BEng, PhD, Sandra Sordon BEng, PhD, Aleksandra Wilczak BEng, PhD and Kinga Sala BEng, MSc. – Our extensive experience in working on the border of biology and chemistry, particularly on the enzymatic and chemical "decorating" of flavonoids to increase their biological potential, resulted in including our team in the project as a scientific partner. Our task is to develop efficient and selective modules for functionalizing flavonoids (microorganisms with properly programmed biosynthesis pathways), compatible with microbial consortia synthesizing these compounds, basing on synthetic biology methods. The resulting optimized modules will also be used as separate tools for the efficient production of a wide panel of modified (e.g. glycosylated) flavonoids. The compounds we receive will serve as models for the research conducted by other project members, and will also undergo comprehensive biological studies – explains prof. Ewa Huszcza, the head of the research team, and adds that the implementation of the tasks entrusted to her team required establishing at the Department of Chemistry, the Genetic Engineering Section, headed by Jarosław Popłoński.

Thanks to the acquired European funds, the section has been fitted with the latest equipment allowing the scientists to carry out work in the field of molecular biology and genetic engineering, and thus to conduct innovative research. An unquestionable benefit coming from the participation in the SynBio4Flav project is also the possibility of international cooperation, including carrying out research at renowned European scientific units. So far this opportunity has been used by Sandra Sordon BEng, PhD and Jarosław Popłoński BEng PhD, who spent a total of 7 months with the project leader.

The project has a Twitter account, its progress can also be followed on the SynBio4Flav website.