Preface Free

With this volume RSC launches a new series of annual reports aiming to keep abreast of current and emerging developments in synthetic biology. Synthetic biology is a new area of interdisciplinary research which combines science and engineering in order to design and build novel biology. Therefore, the definition of synthetic biology has been generally accepted as the engineering of biology: the synthesis of complex, biologically based (or inspired) systems, which display functions that may not exist in nature. This engineering perspective may be applied at all levels of biological hierarchy from individual molecules to cells, tissues and organisms. As with any multi-disciplinary field, there is a substantial and rapidly growing body of literature concerning synthetic biology, with several specialist journals now available. However, finding the best information or identifying the hottest topics in this burgeoning field can be time-consuming. In this vein, this series presents critical and comprehensive reviews of the recent literature in themed chapters prepared by invited authors from around the globe. Each volume strives to highlight the most recent findings and developments in specific research areas and reviewes literature predominantly published over the last two-three years. Routine revisions of more traditional concepts in the light of emerging discoveries, and vice versa, constitute an integral part of each chapter, which makes this series unique and different from other publications and allows keeping pace with the progress without losing touch with foundations.

This first volume starts with an “initiation” into the new field by discussing “expanded DNA” or xDNA and a “new genetic system” in the light of engineering artificial genes (Harcourt and Kool). The discussion particularly stresses upon synthetic and structural aspects of designer DNA bases and base pairs, genetic sets and their biologically relevant activities, culminating with a critical overview of xDNA replication for future studies in synthetic biology. A subsequent focus, logically and synthetically, is made in the following chapter (Bosmans and Brunsveld), which describes post-translational modifications of proteins and their impact on the regulation of complex cellular networks. The chapter extends the notion of a biological toolbox to protein and peptide construction and addresses the importance of designer amino acids enabled by semi-synthetic and chemical approaches. The argumentation for the intrinsic role of proteins as indispensible synthetic blocks is further developed with a principal emphasises made on functional integration of proteins with biology and engineered biological systems (Dalby). A stronger focus here is made on directed evolution strategies, their comparison and relevance to the creation of de novo metabolic pathways as well as novel animo acids, DNA and RNA. The re-use and re-purposing of biological function mediated by RNA editing is then described from the perspective of genetic circuits, genome regulaton, protein recognition and complex assemblies, with an intimate connection made to the re-engineering of the genetic code (Filipovska and Rackham). The next chapter follows the trend and comprehensively reviewes synthetic biology of the code (Suga, Hipolito, Goto, Katoh, Bashiruddin), which starting from non-standard aminoacyl-tRNAs and sense codon re-assigments covers methodological developments for the re-programming of the genetic code to enable the synthesis of complex bioactive peptides, both natural and synthetic. Three subsequent chapters take a step up in the hierarchical origin of synthetic biology and address the challenge of exploitable strategies for modular protein design. Firstly, pros and cons in the development of protein sensors and switches are outlined in terms of inter-relationships between design modularity and functional integration exemplified by minimalistic protein architectures (Merkx). This is followed by de novo extracellular approaches devised to instruct cell biology using synthetic cell-supporting matrices. Specific highlights include modular design principles learned from the functional feedback between matrix “niches” and cellular development (Ryadnov). The discussion continues with how the reproducible and discrete nanostructured morphologies of protein assemblies including viral, bacterial and non-viral encapsulators and protein cages define fundamental biological functions and hence applications, ranging from intracellular delivery and trafficking to catalysis (Brasch, Cornelissen, Koay). Engineering functional interfaces which go beyond specialist biomolecular classes, be these nucleic acids or proteins, bring the complexity of synthetic biology a further step up (Marsden and Kros). Important interfacial elements of native machinery, membranes, are reviewed as an enabling tool for the bottom-up synthesis of life the feasiblity of which is probed through functional biomimicry, compartmentalisation, replication and transport. Providing synthetic membranes neatly leads to the concept of a synthetic cell and first of all to methods and technologies that can make it possible. Lipid-based microfluidic devices are discussed as a promising means to deliver cell-like characteristics ranging from cytosolic encapsulation and controlled membrane permeability for cell-free protein expression and regulation to high-throughput generation of model and customised artificial cells (Osaki, Kamiya, Takeuchi). How such and other functionalities can be constructed is discussed in the pen-ultimate chapter along the lines of chemical synthetic biology with major efforts given to the synthesis of chemical structures that are alternative to those existing in Nature (Chiarabelli, Stano, Luisi). Examples under discussion include “never-born” biopolymers such as peptide nucleic acids (PNA), de novo RNA and proteins and minimal autopoietic cells (capable of self-production) that are constructed from liposomes incorporating synthetic genomes to support simple biochemical networks mimicking metabolic pathways. Finally, an application overview of re-engineered naturally occuring metabolic pathways to rationally control the channeling of metabolic fluxes towards specific targets concludes this volume (Møller). Light-driven synthesis and the construction of supramolecular metabolons are presented as a radical step change to disruptive innovation which is already beginning to produce high-value products.

Each chapter is structured around current trends in the reviewed research area that are compared with more established approaches wherever possible, and the authors’ outlook of future perspectives, either as a separate section or incorporated in the text. All chapters are written by leading researchers in their subject areas to enable a worldwide information source of broad appeal to researchers in academia and industry.