Heterogeneous catalysis in racemization and kinetic resolution along a journey in protein engineering
العنوان: | Heterogeneous catalysis in racemization and kinetic resolution along a journey in protein engineering |
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المؤلفون: | Görbe, Tamás, 1988 |
المساهمون: | Bäckvall, Jan-Erling, Professor, Hollmann, Frank, Associate Professor |
مصطلحات موضوعية: | racemization, protein engineering, kinetic resolution, heterogeneous catalysis, biohybrid catalyst, organisk kemi, Organic Chemistry |
الوصف: | The first part of my thesis concerns the use of heterogeneous acidic resins for racemization of tert-alcohols without any side-product formation. The focus was to develop a system which can be further extended to a DKR protocol consisting of an enzymatic KR reaction. Based on our knowledge of the resins, an unexpected migratory DKR protocol turned out to be an efficient method for the synthesis of carbocyclic allylic carbinols.The development of enzyme and metal catalyst hybrids was already an ongoing theme in our group. A supporter-free biohybrid catalyst was developed which can be used in several different types of reactions. The Pd(0)-CalB CLEA catalyst was applied in a two-step-cascade transformation and in the DKR of benzylic primary amines. The catalyst was characterized by different analytical techniques, to understand its composition and structure.The enzymes have always been the main focus of the studies and therefore wild type enzymes were initially utilized. However, these natural biocatalysts are associated with certain limitations. In contrast, protein engineering allows for enzymes to be modified and optimized. We have used the technique to create a subtilisin Carlsberg mutant, which was studied both by modeling and in vitro. The mutant was found to catalyze the (S)-selective transesterification of sec-alcohols containing long aliphatic carbon chains, and it also exhibited higher performance in organic solvent.The last project concerned the protein engineering of CalA enzyme towards tert-alcohols. The kinetic resolution of tert-alcohols with this enzyme is very slow but it occurs with good enantioselectivity. The aim was therefore to improve the activity of CalA via protein engineering. Seven amino acids were mutated close to the active site and a library was created based on our prediction. Throughout the screening, a few variants showed higher activity, which were sequenced and further analyzed in the transesterification of tert-alcohols. |
وصف الملف: | electronic |
URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-153921 https://su.diva-portal.org/smash/get/diva2:1188639/PREVIEW01.jpg https://su.diva-portal.org/smash/get/diva2:1188639/FULLTEXT01.pdf |
قاعدة البيانات: | SwePub |
ردمك: | 917797185X 9177971868 9789177971856 9789177971863 |
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