Modern Biocatalysis Advances Towards Synthetic Biological Systems Catalysis Series Series editors: Bert Klein Gebbink, Utrecht University, The Netherlands Jose Rodriguez, Brookhaven National Laboratory, USA Titles in the series: 1: Carbons and Carbon Supported Catalysts in Hydroprocessing 2: Chiral Sulfur Ligands: Asymmetric Catalysis 3: Recent Developments in Asymmetric Organocatalysis 4: Catalysis in the Refining of Fischer–Tropsch Syncrude 5: Organocatalytic Enantioselective Conjugate Addition Reactions: A Powerful Tool for the Stereocontrolled Synthesis of Complex Molecules 6: N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient Synthetic Tools 7: P-Stereogenic Ligands in Enantioselective Catalysis 8: Chemistry of the Morita–Baylis–Hillman Reaction 9: Proton-Coupled Electron Transfer: A Carrefour of Chemical Reactivity Traditions 10: Asymmetric Domino Reactions 11: C–H and C–X Bond Functionalization: Transition Metal Mediation 12: Metal Organic Frameworks as Heterogeneous Catalysts 13: Environmental Catalysis Over Gold-Based Materials 14: Computational Catalysis 15: Catalysis in Ionic Liquids: From Catalyst Synthesis to Application 16: Economic Synthesis of Heterocycles: Zinc, Iron, Copper, Cobalt, Manganese and Nickel Catalysts 17: Metal Nanoparticles for Catalysis: Advances and Applications 18: Heterogeneous Gold Catalysts and Catalysis 19: Conjugated Linoleic Acids and Conjugated Vegetable Oils 20: Enantioselective Multicatalysed Tandem Reactions 21: New Trends in Cross-Coupling: Theory and Applications 22: Atomically-Precise Methods for Synthesis of Solid Catalysts 23: Nanostructured Carbon Materials for Catalysis 24: Heterocycles from Double-Functionalized Arenes: Transition Metal Catalyzed Coupling Reactions 25: Asymmetric Functionalization of C–H Bonds 26: Enantioselective Nickel-catalysed Transformations 27: N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient Synthetic Tools, 2nd edition 28: Zeolites in Catalysis: Properties and Applications 29: Biocatalysis: An Industrial Perspective 30: Dienamine Catalysis for Organic Synthesis 31: Metal-free Functionalized Carbons in Catalysis: Synthesis, Characterization and Applications 32: Modern Biocatalysis: Advances Towards Synthetic Biological Systems How to obtain future titles on publication: A standing order plan is available for this series. A standing order will bring delivery of each new volume immediately on publication. For further information please contact: Book Sales Department, Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge, CB4 0WF, UK Telephone: þ44 (0)1223 420066, Fax: þ44 (0)1223 420247 Email: [email protected] Visit our website at www.rsc.org/books Modern Biocatalysis Advances Towards Synthetic Biological Systems Edited by Gavin Williams North Carolina State University, USA Email: [email protected] and Me´lanie Hall University of Graz, Austria Email: [email protected] Catalysis Series No. 32 Print ISBN: 978-1-78262-726-5 PDF ISBN: 978-1-78801-045-0 EPUB ISBN: 978-1-78801-453-3 ISSN: 1757-6725 A catalogue record for this book is available from the British Library r The Royal Society of Chemistry 2018 All rights reserved Apart from fair dealing for the purposes of research for non-commercial purposes or for private study, criticism or review, as permitted under the Copyright, Designs and Patents Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may not be reproduced, stored or transmitted, in any form or by any means, without the prior permission in writing of The Royal Society of Chemistry or the copyright owner, or in the case of reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of the licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to The Royal Society of Chemistry at the address printed on this page. Whilst this material has been produced with all due care, The Royal Society of Chemistry cannot be held responsible or liable for its accuracy and completeness, nor for any consequences arising from any errors or the use of the information contained in this publication. The publication of advertisements does not constitute any endorsement by The Royal Society of Chemistry or Authors of any products advertised. The views and opinions advanced by contributors do not necessarily reflect those of The Royal Society of Chemistry which shall not be liable for any resulting loss or damage arising as a result of reliance upon this material. The Royal Society of Chemistry is a charity, registered in England and Wales, Number 207890, and a company incorporated in England by Royal Charter (Registered No. RC000524), registered office: Burlington House, Piccadilly, London W1J 0BA, UK, Telephone: þ44 (0) 207 4378 6556. For further information see our web site at www.rsc.org Printed in the United Kingdom by CPI Group (UK) Ltd, Croydon, CR0 4YY, UK Preface Biocatalysis—the use of enzymes for chemical transformations—has a long history in providing mankind with all sorts of molecules. While early processes almost exclusively relied on naturally occurring whole-cell sys- tems, the implementation of molecular biology-based methods has rendered the manipulation of isolated enzymes routine work. This in turn has led to improved knowledge about enzymatic mechanisms and boosted enzyme- orientated research in multiple areas. The past years have seen impressive advances leading to sophisticated tools and innovative techniques for the design and development of bio-based processes for the production of (fine) chemicals. The synergy between synthetic biology and biocatalysis is now strongly emerging as an important trend for future sustainable processes and we felt the need to merge these two complementary branches, which have been evolving mainly concurrently. Excellent books are available for chemists wishing to implement natural catalysts in synthetic processes, while recent books on synthetic biology focus on bottom-up creation of new modular parts, circuit design, and chassis engineering but are not enzyme centric. Specialized and focused reviews in prominent journals on the development of robust and efficient biosynthetic routes are becoming more frequent, but a unifying platform was still missing. This book includes a number of contributions to document the current merging of traditional biocatalysis with more syn- thetic biology-based approaches, and keeps enzymes as the central protagonists. The book is organized into five sections. In Section I, Accessing New Enzymes, several contributions exemplify the technical diversity at hand to identify new enzymes, which largely benefits from ever-improving compu- tational power. In Section II, Understanding and Engineering Enzymes,we gathered experts to highlight how modifying protein sequence and structure Catalysis Series No. 32 Modern Biocatalysis: Advances Towards Synthetic Biological Systems Edited by Gavin Williams and Me´lanie Hall r The Royal Society of Chemistry 2018 Published by the Royal Society of Chemistry, www.rsc.org vii viii Preface in silico and in vivo is fundamental to obtaining crucial catalytic insights used to tailor enzyme properties. In Section III, Enzymes from Secondary Metabolism, several contributions highlight the remarkable ability of enzymes in secondary metabolism to construct complex natural products from simple small molecule building blocks. Approaches to engineer and optimize these pathways are also described. Section IV, Biocatalysis for Modern Synthesis, focuses on elaborate enzyme-based processes developed for the synthesis of fine chemicals. Importantly, multi-step reactions now combine various types of (bio)catalysts and are particularly well suited for the cost-effective generation of enantiopure molecules of high value. Finally, Section V, Applied Biocatalysis, reflects the technological input required to implement natural or engineered enzymes in industrial settings, and finishes with an opening on the promising use of enzymes in remediation, according to which biodegradation processes might witness a restored interest. We hope that readers will find this book helpful to connect all areas that biocatalysis—and synthetic biology—as progressive field now encompasses, and to identify current and emerging trends towards the development of efficient synthetic biological systems in a broad sense. We thereby hope to trigger mutual inspiration for the currently unfolding generation of hybrid chemists/biologists who are committed to render current and upcoming synthetic processes more sustainable. Tools exist, let’s use them! Me´lanie Hall (Graz, Austria) Gavin Williams (Raleigh, USA) Contents Section I: Accessing New Enzymes Chapter 1 Genome Mining for Enzyme Discovery 3 Anne Zaparucha, Ve´ronique de Berardinis and Carine Vaxelaire-Vergne 1.1 Introduction 3 1.2 Text-based Searches Using Enzyme Name 5 1.3 Sequence-driven Approaches 7 1.3.1 Probe Technology Based on PCR Primer Design 7 1.3.2 Pairwise Sequence Alignment-based Strategy 8 1.3.3 Signature-/Key Motif-based Strategy 15 1.4 3D Structure-guided Approach 18 1.4.1 Exploring 3D Structures of Proteins 19 1.4.2 Active Site Topology/Constellation-guided Strategy 19 1.5 Conclusion 22 References 23 Chapter 2 Exploiting Natural Diversity for Industrial Enzymatic Applications 28 Yasuhisa Asano and Richard Metzner 2.1 Introduction 28 2.2 Screening Enzymes