Publication

Designing artificial enzymes with unnatural amino acids

Drienovská, I. 2017 [Groningen]: University of Groningen. 147 p.

Research output: ScientificDoctoral Thesis

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  • Title and contents

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  • Chapter 1

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  • Chapter 2

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  • Chapter 3

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  • Chapter 4

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  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Nederlandse samenvatting

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  • Acknowledgments

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  • Complete thesis

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  • Propositions

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Enzymes are powerful biocatalyst that play a central role in all biological reactions in nature. They are known to catalyze reactions with high activity and remarkable selectivity, however they are sensitive to the environment and exhibit limited scope for substrates and reactions. Hence, efforts have been devoted to develop an alternative to natural enzymes, called artificial enzymes, which would act with the same efficiency, but exhibit valuable advantages over natural systems, like activities towards new-to-nature reactions. This would be of great practical interest, with potential applications in industrial processes.
This thesis describes the development of a novel methodology to create artificial enzymes utilizing genetically encoded unnatural amino acids. Unnatural amino acids are known to feature a wide range of side chains and functional groups therefore offer great opportunities to expand the toolbox of artificial enzymes. A major part of this thesis describes the application of this methodology for creating novel artificial metalloenzymes, introducing different metal-binding amino acids, (2,2΄-bipyridin-5-yl)alanine and (8-hydroxyquinolin-3-yl)aniline into the structure of transcription regulator LmrR. These novel metalloenzymes have proven successful in catalysis of challenging reactions, such as Friedel-Crafts alkylation reaction or enantioselective water addition and showed potential for others. Furthermore, the non-metal binding p-aminophenylalanine was used as catalytic residue for a novel class of enzymes. Utilizing the nucleophilicity of aniline in the side chain of this unnatural amino acid, an artificial enzyme was prepared that was able to catalyze hydrazone formation reactions, which represents a novel type of the catalysts for a reaction not known to nature so far.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date23-Jun-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-9826-6
Electronic ISBNs978-90-367-9825-9
StatePublished - 2017

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