Pioneering the Frontier of Enzyme Research for Biotechnology Advancements: Exploring the Uncharted Territory of Flavin-dependent Enzymes and Envisioning a Future Driven by AI-approaches
With a focus on redox enzymes, particularly flavin-dependent enzymes, Prof. Marco Fraaije has developed expertise in this fruitful field. His fascination with these enzymes traces back to the research project at the University of Wageningen, mentored by Prof. Willem van Berkel. Today, together with his team, Marco is on a pursuit of knowledge that is paving the way for transformative changes across industries.
“Studying these enzymes is like catching a case of yellow fever,” Marco jokes, referring to the vibrant yellow hue exhibited by the bound flavin cofactor. “Yet, it’s not the color that attracted my attention; it’s the remarkable catalytic versatility of flavoenzymes and the enigmatic interplay between the protein component and their catalytic properties.” This group of proteins relies on a flavin cofactor, an extremely versatile molecule capable of undergoing oxidation–reduction reactions by exchanging either one or two electrons. Consequently, flavoenzymes can catalyze a plethora of reactions. Due to the versatility of products, these enzymes have been applied in various applications, such as biocatalysts in synthetic processes for the chemical and pharmaceutical industries.
Fuelled by curiosity, Fraaije’s research group studies the intricate mechanisms by which these enzymes and other cofactor-dependent counterparts catalyze reactions. With these findings, they aim to optimize their use in industrial applications through knowledge-based enzyme engineering. Marco underscores, “By deciphering the inner workings of flavoenzymes, we hope to unleash their full potential for industrial purposes.”
Around 2017, Marco began to receive an increasing number of inquiries regarding enzymes and rare cofactors. While these enzymes were documented in scientific literature, they remained largely inaccessible to interested parties, with samples only obtainable through Fraaije’s research group. This surge of interest from biotech companies, research institutes, universities, and even schools sparked a realization - “When I saw the growing demand for enzymes and cofactors, I wondered if this apparent market need could be the foundation for a company.”, Marco reflects. “Coincidentally, this idea aligned with the aspirations of one of my post-doctoral researchers, Nikola Lončar, and together, we embarked on an exciting journey with the GECCO initiative.”
Another source of excitement for Marco Fraaije lies in the intersection of scientific exploration and technological progress. “The progress we’ve witnessed in recent years, particularly in machine learning and enzyme research, is nothing short of extraordinary,” he remarks about the emerging possibilities. He describes that machine learning algorithms can now predict a protein’s three-dimensional structure solely based on its sequence, a feat once considered unfathomable. Beyond structural predictions, these powerful tools extend their influence on substrate specificity and even kinetics, forging new pathways in enzyme discovery and design.
“The advent of data-driven approaches in assisting with enzyme discovery, engineering, and even design marks an exciting era,” Marco concludes. “Identifying yet-to-be-discovered enzymes remains an attractive prospect, and these methods offer an avenue for exploration. Additionally, the ability to design enzymes specifically for desired, even unconventional reactions presents abundant possibilities in biotechnology.”
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