A new European project combines artificial intelligence and synthetic biology to obtain plant compounds

The Spanish National Research Council (CSIC) is participating in Decypher, a new European project that proposes to merge synthetic biology with artificial intelligence and machine learning to produce terpenoids and flavonoids, natural compounds found in small quantities in plants that can be used in industrial biotechnology.

The Systems Biotechnology Group of the National Biotechnology Center (CNB-CSIC), led by Juan Nogales, and the Polymer Biotechnology Group of the Margarita Salas Center for Biological Research (CIB-CSIC), led by Auxiliadora Prieto, are members of this initiative funded with 6 million euros, which integrates 10 groups from 6 European countries.

These two teams will work in coordination to optimize the expression and performance of plant enzymes (called CYP), responsible for the production of terpenoids and flavonoids in synthetic microbial compartments specially designed for this purpose. In addition, CSIC is leading efforts to redirect the metabolic pathways of Pseudomonas putida, one of the bacterial species of greatest industrial interest, for the production of functional flavonoids, thus obtaining highly efficient microbial cell factories.

"Advances in artificial intelligence and machine learning narrow down design possibilities to the most likely ones and can discover novel solutions for nature," said Marjan De Mey, a researcher at Ghent University (Belgium) and coordinator of the project.

In addition to its contribution to decoding the basic components and processes of nature, Decypher will apply an innovative and holistic approach to the development of bioprocesses. Within the framework of the project, the scientists will develop a standardized artificial intelligence and machine learning platform for biotechnological applications, as well as guide bioprocesses through all steps of the development chain. Based on specific targets for case studies (and decoding CYP), Decypher plans to work methodically to take bioprocess design and control beyond an art form to a reproducible and sustainable system.

Flavonoids and terpenoids

Terpenoids and flavonoids are traditionally extracted from plants and have received much attention due to their importance for various applications and markets, such as pharmaceuticals, fragrances and flavors, food preservatives, and insecticides. Their diversity is due to the many variations in common molecular structures, most of which are derived from oxygenation carried out by a large family of enzymes called cytochromes P450 (or CYP).

However, only a small fraction of these compounds can be extracted commercially from plants and, due to their low content in plants, these commercial processes require large-scale cultivation that is unsustainable. Terpenoids and flavonoids illustrate once again the complexity involved in biological processes and the difficulty of decoding and re-engineering them in a laboratory, not to mention their production on an industrial and commercial scale.

Decypher is a Horizon Europe project funded with €6 million that was launched on September 1, 2023, and will run for the next four years. The project is coordinated by Ghent University and brings together 10 partners from 6 European countries: 5 research and technology organizations (UGent, CSIC, Stichting Wageningen Research, Barcelona Supercomputing Center, VIB), 3 small and medium-sized companies (ML6 Skyhaus, Biofaction, Lantana Bio), a large company (Isobionics) and an association dedicated to the promotion of art and natural sciences (Finnish Bioart Society).