Engineering the Genetic Code: Expanding the Amino Acid Repertoire for the Design of Novel Proteins

The ability to introduce non-canonical amino acids in vivo has greatly expanded the repertoire of accessible proteins for basic research and biotechnological application. Here, the different methods and strategies to incorporate new or modified amino acids are explained in detail, including a lot of practical advice for first-time users of this powerful technique. Novel applications in protein biochemistry, genomics, biotechnology and biomedicine made possible by the expansion of the genetic code are discussed and numerous examples are given. Essential reading for all molecular life scientists who want to stay ahead in their research.

Table of Contents:
INTRODUCTION Classical Approaches for Protein Modification Protein Total Synthesis Basic Definitions and Taxonomy HISTORY OF AN EXPANDED AMINO ACID REPERTOIRE Cell-free Synthesis of Proteins Noncanonical Amino Acids as Tools for Studying Metabolism Genetic Code Engineering BASIC FEATURES OF THE CELLULAR TRANSLATION APPARATUS Ribosome-mediated Protein Synthesis tRNAs and tRNA Synthetases Translational Proofreading Ribosomal Decoding, Codon Bias and Translational Fidelity Context-dependent Recoding Post-translational Modifications GENETIC CODE ORGANISATION AND PROTEIN STRUCTURE The Universal Genetic Code Natural Variations in Codon Assignment Codon Reassignment and Codon Ambiguity REPROGRAMMING THE CELLULAR TRANSLATION MACHINERY Enzyme Specificity and Code Interpretation Reassigning Coding and Non-Coding Units In vitro Chemical and Enzymatic tRNA Aminoacylation Novel Codon-Anticodon Base Pairs Stop Codon Takover Suppression-Based Methods Future Approaches IMPLICATIONS AND INSIGHTS Evolution of the Amino Acid Repertoire Artificial Genetic Systems De novo Design of Organisms Chances and Risks APPLICATIONS FOR REPROGRAMMED CELLULAR TRANSLATION Genetically Encoded Protein Surface Diversity Applications in Structural Biology Atomic Mutations Protein Folding, Stability and Design Tailoring Protein Spectroscopy Protein-based Sensors Applications in Biomedicine Noncanonical Amino Acids with Neurological Activity

About the Author :
Nediljko Budisa is a group leader at the Max-Planck-Institute of Biochemistry in Martinsried near Munich (Germany). He studied Chemistry and Biology at the University of Zagreb (Croatia) before joining the group of Nobel Prize Winner Robert Huber at Martinsried to obtain his PhD degree. During postdoctoral work with R. Huber and L. Moroder he led an independent research team in protein engineering. In 2004, Dr. Budisa received the BioFuture Award of the German Federal Ministry for Research and Education.

Review :
"In his book, Nediljko Budisa covers this highly interdisciplinary field and allows people not directly involved in protein engineering to get acquainted and up-to-date with the most recent and exciting developments. The book, which is the first of its kind dedicated entirely to this area of research, provides a comprehensive overview of the field. The book comprises seven chapters and has a clear structure supported by a multitude of fine illustrations, thus making the book a good read for those interested in protein engineering. ... Moreover, an excellent update on protein translation in general is given, which is useful for students and newcomers in the field. (...) The book provides an excellent introduction for first-time readers to the field of genetic-code engineering and, as stated on the back of the book, this is 'essential reading to all molecular life scientists who want to stay ahead in their research'." ChemBioChem "The numerous examples illustrate the new prospects that are opened up by genetic code engineering. We can expect novel proteins with properties that cannot be foreseen in detail, when one considers that, even for polypeptides based on the 20 proteinogenic amino acids, the rules of folding are still not known." Angewandte Chemie International Edition "...besticht das Buch durch seine terminologische Klarheit und transdisziplinäre Kompetenz. Es dürfte ein Gewinn sein sowohl für Interessierte an aktuellen Methoden der Molekularbiologie als auch für jene, die von der Wandelbarkeit des "universellen" genetischen Codes einfach fasziniert sind." Nachrichten aus der Chemie "Die umfangreiche Zahl der Beispiele belegt die neue Dimension, die das Code-Engineering erschließt. Wir können neuartige Proteine mit nicht vorhersehbaren Eigenschaften erwarten, zumal schon für Polypeptide mit den 20 proteinogenen Aminosäuren der Faltungscode ungelöst ist. Aber auch Fragen zu neuen Einsatzfeldern in Technik und Pharmakologie, zur Evolution des genetischen Codes und zur Ethik der tiefgreifenden Veränderungen, die das Code-Engineering ermöglicht, werden behandelt." Angewandte Chemie "Wer sich über diese brisante Materie informieren möchte, ist mit dem konkurrenzlosen Standardwerk von Budisa exzellent beraten." Das Science Fiction Jahr - Wissenschaftsbücher 2005