Decoding the enzymatic closure of alginates for green biotechnology

Decoding the enzymatic closure of alginates for green biotechnology

Every year, thousands of tons of brown algae are extracted from the seabed to obtain compounds such as alginates, a polymer of sugars with high density and strength that offer potential biotechnological applications. An international team from the University of Barcelona has deciphered the mechanism by which a type of enzyme called alginate lyase (AL) is able to degrade these marine biomaterials, allowing them to be used as drug carriers, additives or thickeners, among other things. These results, published inNature communicationwill help develop and design new “tailor-made alginates” for specific applications, particularly in the food and biomedical industries.

The UB team is founded by José Pablo Rivas-Fernández, first author of the article, and Carme Rovira, ICREA Research Professor, from both the UB Faculty of Chemistry and the UB Institute of Theoretical and Computational Chemistry (IQTCub) (Dtukens, BIOTECHS, BIOTIC CHEMISTRY). Experts from the Norwegian University of Science and Technology (NTNU) and North Carolina State University (USA) also took part.

Despite the abundance of alginates in the marine environment, their potential, especially in the biomedical sector, is severely limited by the inhomogeneity of their composition in the natural state - they can contain a mixture of mannuronic and guluronic sugars in different proportions. Knowledge of the mechanism of action of Al enzymes when they specifically break the bonds connecting the mannuronic acid-type sugar in this polymer helps to overcome these limitations. “The results laid the foundation 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 “tailor-made alginates” in sufficient quantities to meet the needs of society, “explain the researchers.

These findings also enable “better use of natural resources and increase the green economy by using enzymes as key tools in the production of these alginates,” say the authors.

Computer analysis with the Marenostrum 5 supercomputer

Part of the study was based on the computational analysis of the mechanism of action of these enzymes, using 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 Alginate.

These simulations have reconciled previous scientific discrepancies about the number of stages in which the reaction occurs, confirming that it occurs in a single stage and that the polymer breaks in the middle, not at one end. They also clarified 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 mutating certain amino acids in the active site of the enzyme,” the researchers explain.

Another important element of the study is that the enzymes analyzed belong to family 7 of lyases, the most commonly known to date, allowing extrapolation of the mechanism that has described other enzymes with high biotechnological potential.

These results also facilitate the identification of important residues or amino acids aimed at improving the efficiency of these enzymes, a promising line of research that the UB team is already working on.

In addition, the results improve the understanding of the chemical evolution of alginate during its degradation, a fundamental element for the design of probes that can identify and isolate alginate lyases that have not yet been described. With this in mind, UB researchers are currently working on the design of probes that enable the efficient identification of new enzymes 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 research teams working together to solve important scientific challenges.

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