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University of Groningen Lanthipeptide engineering: non-canonical amino acids, click chemistry and ring shuffling Deng, Jingjing

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University of Groningen

Lanthipeptide engineering: non-canonical amino acids, click chemistry and ring shuffling

Deng, Jingjing

DOI:

10.33612/diss.112973724

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Deng, J. (2020). Lanthipeptide engineering: non-canonical amino acids, click chemistry and ring shuffling.

University of Groningen. https://doi.org/10.33612/diss.112973724

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Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

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Lanthipeptide engineering:

non-canonical amino acids, click chemistry and ring shuffling

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The work described in this thesis was performed in the Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Faculty of Science and Enigineering (FSE), Uni-versity of Groningen, the Netherlands, and financially supported by the China Scholarship Council (CSC). Printing of this thesis was financially supported by the Graduate School of Science and Engineering and the University of Groningen.

Cover: Jingjing Deng

Layout: Lovebird design. www.lovebird-design.com Printed by: Eikon +

ISBN: 978-94-034-2356-2 (printed version) ISBN: 978-94-034-2355-5 (electronic version) Copyright @J. Deng, Groningen, the Netherlands, 2020

All rights reserved. No part of this thesis may be reproduced in any form or by any means without prior permission of the author.

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3

Lanthipeptide engineering:

non-canonical amino acids, click chemistry

and ring shuffling

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 3 February 2020 at 9.00 hours

by

Jingjing Deng

born on 20 August 1990 in Anhui, China

3

Lanthipeptide engineering:

non-canonical amino acids, click chemistry

and ring shuffling

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 3 February 2020 at 9.00 hours

by

Jingjing Deng

born on 20 August 1990 in Anhui, China

3

Lanthipeptide engineering:

non-canonical amino acids, click chemistry

and ring shuffling

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 3 February 2020 at 9.00 hours

by

Jingjing Deng

born on 20 August 1990 in Anhui, China

3

Lanthipeptide engineering:

non-canonical amino acids, click chemistry

and ring shuffling

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 3 February 2020 at 9.00 hours

by

Jingjing Deng

born on 20 August 1990 in Anhui, China

3

Lanthipeptide engineering:

non-canonical amino acids, click chemistry

and ring shuffling

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 3 February 2020 at 9.00 hours

by

Jingjing Deng

born on 20 August 1990 in Anhui, China

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4

Supervisor

Prof. O.P. Kuipers

Coo-supervisor

Prof. J. Kok

Assessment Committee

Prof. G.N. Moll

Prof. J.G. Roelfes

Prof. N.I. Martin

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Contents

Chapter 1 General introduction ...7

Chapter 2 Specificity and application of the lantibiotic protease NisP ...23

Chapter 3 Analysis of modular bioengineered antimicrobial lanthipeptides

at nanoliter scale ...53

Chapter 4 Generation of nisin derivatives with an altered spectrum by

incorporating methionine analogues ...107

Chapter 5 Synthesis of nisin conjugates via click chemistry and their

char-acterization ... 129

Chapter 6 Summary and general discussion ... 149

Nederlandse samenvatting ...157

Acknowledgments ... 159

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