Computational design of industrial enzymes for green chemistry

Projektinformationen

GREENZYME

ID Finanzhilfevereinbarung: 101112805

DOI

10.3030/101112805

Projekt abgeschlossen

EK-Unterschriftsdatum 24 Februar 2023

Startdatum 1 Mai 2023

Enddatum 31 Oktober 2024

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

UNIVERSITAT DE GIRONA
Spain

Periodic Reporting for period 1 - GREENZYME (Computational design of industrial enzymes for green chemistry)

Berichtszeitraum: 2023-05-01 bis 2024-10-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Catalysts are able to reduce activation barriers of reactions making them possible at lower pressure an temperatures. Enzymes are the most efficient, specific, and selective catalysts known. Green chemistry has emerged as a new area focusing on use of environmentally friendly, non-hazardous and efficient solvents and catalysts in the synthesis of new products. Enzymes are non-toxic, and capable of operating under mild biological conditions, which makes them green catalysts offering an attractive alternative to traditional catalysis. However, their application in industry is rather limited as most industrial processes lack a natural enzyme. The solution is the routine design of enzymes, but this task has not yet been achieved due to several limitations, such as the high complexity of enzyme catalysis, the lack of accurate computational approaches for designing and estimating the catalytic potential of the new variants, and the inability to identify potential mutation sites far away from the active site of the enzyme. GREENZYME provides a new protocol able to capture this high complexity and design new enzymes capable of predicting active site and distal mutations, thus achieving high levels of activity (as it would occur in nature). This is achieved by integrating current Shortest Path Map-Ancestral Sequence Reconstruction (SPM-ASR)-based computational protocol developed in previous projects such as the ERC-StG NetMoDEzyme with deep learning techniques. Thanks to a well-thought-out exploitation and communication strategy, the premise of routine enzyme design is possible. This has a large-scale socio-economic impact, as it reduces the production costs of many drugs, while allowing industries to use environmentally friendly alternatives in line with new European policies.

The main objectives of GREENZYME are:
O1 - Integration of the current SPM-based computational protocol with DL techniques
O2 - Intellectual Property (IP) plan
O3 - Market research and search for additional technological partners
O4 - Strengthening of the knowledge transfer and entrepreneurship of the team through training activities
O5- Maximising GREENZYME impact

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Activity 1: Integration of the current SPM-based computational protocol with DL techniques. We have combined the SPM-based approach developed in the ERC-StG project with the DL technique AF2 for its application to computational enzyme design. We have validated the developed methodology in collaboration with different industrial partners.

Activity 2: Development of a webserver with the technology. We have developed a webserver (https://spmosuna.com) that allows non-commercial users to apply our SPM methodology that was already published (Protein Eng. Des. Sel., 2024, gzae005).

Activity 3: Intellectual Property Plan. We have developed an IP plan jointly between the research team, University’s technology transfer unit, ICREA, and a third-party specialized consulting company.

Activity 3: Market research and search for additional technological partners. We have done market research, including a competitive analysis, to search for stakeholders and fit our product and costs to differ from our competitors with the specialized consulting company. We have applied for additional funding from different national (Spanish MINECO and Catalan agency) and an additional ERC-POC grant.

For the future exploitation of our technologies, a spin-off based in Girona will be created. We expect to create the spin-off by the end of 2025. A mixed exploitation model will be carried out in which different services will be offered

Activity 4: Participation in knowledge transfer and entrepreneurship trainning activities. The team has participated in several training activities for fostering entrepreneurship and strengthening knowledge transfer abilities (Cycle of Knowledge Transfer Capsules program at UdG, Collider ON CAMPUS program, 4YFN at the Mobile World Congress).

Activity 5: Maximizing the impact of GREENZYME. The team has publicized the most relevant findings of the project to social media and local newspapers to awaken the interest from academic, industrial partners and the general public. Key plenary and invited lectures have been given at industrial and scientifc (and mixed) conferences (GRC Biocatalysis, Faraday Discussion conference on Biocatalysis, Biocat conference).

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

GREENZYME has developed a proprietary technology for the rational design of enzymes. By proposing modifications and mutations in optimal positions, considering the complete enzyme structure, whether they belong to the catalytic site or are distal, significant performance improvements of up to three orders of magnitude can be achieved. This is accomplished using a short time of simulation and analysis and at a substantially lower cost compared to Directed Evolution. The development of affordable and highly efficient and low cost strategies for designing new biocatalysts is of utmost importance. This will significantly enhance the efficiency and economic viability of creating novel biocatalysts, aligning with new EU policies and market demands, while also reducing computational and energy costs. Notwidthstanding the routinely use of environmentally friendly enzymes in industrial contexts will have a big impact towards a more sustainable world for our future generations.


Thanks to GREENZYME a roadmap for the early valorisation and the market entrance of the technology to a wide number of industries interested in speeding up catalytic processes. However, from the multiple interviews performed with different (bio)chemical and pharmaceutical companies it was clear that the computational technology alone is not sufficient. Based on this fact, a new ERC-POC grant to experimentally generate a set of rationally designed and industrially relevant enzymes with our core technology was requested and awarded (KITZYME, ERC-2023-POC-101158166). We will create a spin-off to commercialize the enzyme kits and offer the service of enzyme design.