Computational study and rational design of pluriZymes
[eng] The increase in production over the last centuries has come at the expense of compromising the environment, urging the need to find solutions. Enzymes are the essential molecules that make life kinetically possible. In industry, enzymes can be a sustainable alternative to using inorganic catal...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/192222 |
| Acceso en línea: | https://hdl.handle.net/2445/192222 http://hdl.handle.net/10803/687423 |
| Access Level: | acceso abierto |
| Palabra clave: | Biocatàlisi Enzims Enginyeria de proteïnes Química verda Enginyeria sostenible Biocatalysis Enzymes Protein engineering Green chemistry Sustainable engineering |
| Sumario: | [eng] The increase in production over the last centuries has come at the expense of compromising the environment, urging the need to find solutions. Enzymes are the essential molecules that make life kinetically possible. In industry, enzymes can be a sustainable alternative to using inorganic catalysts. However, their low productivity, poor resistance to industrial conditions, and their cost limit their usage. Thus, enabling the tailoring of biocatalysts at will is crucial to expand their application. The advances in computational power, followed by the repertoire of modeling tools, are helping design the next generation of biocatalysts due to their lower costs and quickness. This thesis aims to develop a novel concept of biocatalysis, which could lower the expression costs of enzymes, named pluriZymes. PluriZymes are proteins with plural catalytic active sites where one (at least) of them is artificially designed. The type of introduced functional site along the thesis has been the hydrolase one due to its simplicity (only 3 catalytic residues needed) and does not need a cofactor. The studied systems were transaminases and esterases since they have several applications in industry, thus, being of broad interest. All computational designs were experimentally validated by our collaborators. The thesis' results include an in-one protease-esterase pluriZyme, a transaminase- esterase pluriZyme with potential applications for the pharmaceutical industry, the rational improvement of substrate promiscuity of hydrolase sites, and a new algorithm to facilitate the design of artificial active sites. Hence, this thesis proves the potential of pluriZymes for the next generation of biocatalysts toward a more sustainable society and the need for computational tools to develop them. |
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