Robustini, Lucia (2024). Enzyme Application for Chemical Transformations: A Pathway to Green Synthesis. (Thesis). Universität Bern, Bern
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24robustini_l.pdf - Thesis Available under License Creative Commons: Attribution (CC-BY 4.0). Download (6MB) | Preview |
Abstract
Recent efforts to reduce emissions and environmental impacts associated with industrial processes has led to a significant amount of research reporting alternative synthetic methods for industrial and chemical production. Biocatalysis, in particular, has gained an increased amount of interest as a complementary tool to classical chemistries. Biocatalyts often operate under mild reaction conditions, whilst maintaining a high degree of selectivity of product formation. However, the implementation of enzymes at large production scales is not without limitations - challenges include catalyst stability, cofactor reusability, and reaction setup (e.g., in batch processes), all of which necessitate optimization for a cost-effective application. The use of immobilized enzymes and the transition to automated flow systems are two of many solutions which has allowed the expansion of biocatalysis beyond its initial restricted applications. These advancements have enabled gram-scale production of fine chemicals with a high degree of enantiospecificity. In this work, we explore the potential use of biocatalysts for the production of medicinally-important molecules. Several critical aspects for efficient biocatalyst utilization are also investigated. With a meticulous screening of reaction conditions, the control of enantiopreference in an industrially-significant transaminase will be assessed. Factors such as ionic strength, co-solvent, pH, and reaction time are investigated, leading to enhanced or inverted specificity of the final enantiomer. Furthermore, we leverage the use of a proteinaceous cage, a structure identified in bacteria as compartmentalisation structure, as a method for the immobilisation of biocatalysts. This nanocage serves as a protective capsule, effectively preserving the native conformation of the enzyme while simultaneously enhancing its activity due to the localized high substrate concentration within the cage. We thoroughly investigated the impact of the encapsulation of two enzymes. We also further assessed the potential application of immobilization of the nanocage, creating a protective microenvironment for the enzymes – a method that may lead to more efficient industrial processes. Additionally, we explore the combination of enzymatic and chemical processes, highlighting the complementarity of these two approaches to access important molecules. By combining an enzymatic cascade with the final chemical step, we aim to develop a method for the production of valuable psychoactive compounds. The sequential use of two enzymes led to the synthesis of an intermediate which will be converted in the final product, effectively upcycling starting materials and adding value to the overall process. Through these objectives, we aim to expand the role and application of biocatalysis, positioning it as a viable and sustainable choice for environmentally friendly industrial applications.
| Item Type: | Thesis |
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| Dissertation Type: | Cumulative |
| Date of Defense: | 7 May 2024 |
| Subjects: | 500 Science > 540 Chemistry 500 Science > 570 Life sciences; biology |
| Institute / Center: | 08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
| Depositing User: | Hammer Igor |
| Date Deposited: | 09 Sep 2024 12:27 |
| Last Modified: | 10 Sep 2024 02:13 |
| URI: | https://boristheses.unibe.ch/id/eprint/5408 |
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