Every year, thousands of tonnes of brown algae are extracted from the seabed to obtain compounds such as alginates, a polymer composed of sugars that has high density and strength, offering potential biotechnological applications. An international team led by the University of Barcelona has deciphered the mechanism by which a type of enzyme, called alginate lyase (AL), is capable of degrading these marine biomaterials, allowing them to be used as carriers of drugs, additives or thickeners, among others. These results, published in Nature Communications, will help in the development and design of new “tailored alginates” for specific applications, especially in the food and biomedical industries.
The UB team is formed by José Pablo Rivas-Fernández, first author of the article, and Carme Rovira, ICREA research professor, both from the UB’s Faculty of Chemistry and the UB Institute of Theoretical and Computational Chemistry (IQTCUB), in coordination with Casper Wilkens, biotechnologist at the Technical University of Denmark (DTU). Experts from the Norwegian University of Science and Technology (NTNU) and North Carolina State University (United States) have also participated.

Despite the abundance of alginates in the marine environment, their range of opportunities, especially in the biomedical sector, is severely limited by the inhomogeneity of their composition in the natural state — they may contain a mixture of mannuronic acid and guluronic acid sugars in varying proportions. Knowledge of the mechanism of action of AL enzymes when they specifically break the bonds connecting the mannuronic acid-type sugars in this polymer will help to overcome these limitations. “The results lay the groundwork for manipulating these enzymes and designing variants with better catalytic properties and higher efficiency on a large scale.

By using industrial techniques and bioprocesses, it will be possible to optimize the production of ‘tailored alginates’ in sufficient quantities to meet society’s needs”, the researchers explain.
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These findings will also allow for a “better use of natural resources and boost the green economy by using enzymes as key tools in the production of these alginates”, say the authors.

Computational analysis with the MareNostrum 5 supercomputer

Part of the study was based on the computational analysis of the action mechanism of these enzymes, using as a starting point the three-dimensional structures of the AL enzyme in interaction with different alginate variants, obtained by the DTU collaborators. Based on this structure and using the resources of the MareNostrum 5 supercomputer at the Barcelona Supercomputing Center — Centro Nacional de Supercomputación (BSC-CNS), the UB team has carried out molecular dynamics simulations, using multiscale quantum mechanics and molecular mechanics techniques to model and obtain a detailed description at the atomic level of the chemical reaction that takes place during the degradation of alginates.​​​​​​​
These simulations have reconciled previous scientific discrepancies about the number of stages in which the reaction occurs, confirming that it happens in a single stage and that the polymer breaks at the centre, not at one end. They have also cleared the nature of the transition state — the highest energy configuration during the reaction — as a highly negatively charged species. “This finding suggests that we may be able to control at what point the polymer breaks down by mutations of certain amino acids in the enzyme’s active centre”, the researchers explain.

Another important element of the study is that the enzymes analysed belong to family 7 of lyases, the most abundant known to date, which allows extrapolating the mechanism described to other enzymes with high biotechnological potential.

These findings also facilitate the identification of key residues or amino acids that can be targeted to improve the efficiency of these enzymes, a very promising line of research on which the UB team is already working.

Moreover, the results improve the understanding of the chemical evolution of alginate during its degradation, a fundamental element for the design of probes capable of identifying and isolating alginate lyases, which have not yet been described. In this sense, UB researchers are currently working on the design of probes that allow the efficient identification of new enzymes active in carbohydrates.

This study is part of Carbocentre, a project funded by a Synergy Grant from the European Research Council (ERC). These grants are among the most prestigious in Europe and are awarded to teams of researchers working together to tackle major scientific challenges.