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Since its debut in 2000, synthetic biology has grown considerably and now constitutes a vibrant research discipline that promises to transform the world we live in. This Nature Special showcases specially commissioned content from Nature Reviews Microbiology, Nature Methods and Nature, which together charts the progression of the field from the design and construction of simple biological systems through to the development of more sophisticated systems and their applications, as well as the current challenges and opportunities. Together with a selection of related archive content from Nature Research, this Special celebrates the achievements of synthetic biology.
This Focus issue highlights the growth of synthetic biology as a vibrant and vigorous scientific discipline that has its roots firmly grounded in microbiology.
Non-coding RNA devices, such as CRISPR–Cas systems, riboswitches and RNA scaffolds, have emerged as a versatile class of genetic regulatory elements that are used in a broad range of synthetic biology applications. In this Review, Arkin and Qi discuss the design, engineering and application of synthetic non-coding RNA devices for microbial engineering.
Entry of the antimalarial drug precursor semi-synthetic artemisinin into industrial production is the first major milestone for the application of synthetic biology. In this Review, Paddon and Keasling discuss the metabolic engineering and synthetic biology approaches that were used to engineerEscherichia coli and Saccharomyces cerevisiaeto synthesize a precursor of artemisinin, which should aid the development of other pharmaceutical products.
Much of synthetic biology research makes use of model organisms, such asEscherichia coli. Here, Víctor de Lorenzo and colleagues emphasize the need for a wider choice of model organisms and advocate the use of environmental Pseudomonasstrains as model organisms that possess the necessary metabolic traits required to meet current and future synthetic biology and biotechnological needs.
In this Timeline article, Collins and colleagues chart the history of synthetic biology since its inception just over a decade ago, with a focus on both the cultural and scientific progress that has been made as well as on key breakthroughs and areas for future development.
Authors discuss how synthetic biology approaches could be applied to assemble synthetic quasibiological systems able to replicate and evolve, illuminating universal properties of life and the search for its origins.
This Perspective takes the reader through the important steps in bacterial genome assembly and activation and concludes with an outlook on how customized genomes may be achieved.
This Review discusses large-scale de novo DNA synthesis via oligos or arrays, describes gene assembly and error correction and considers applications for large-scale DNA synthesis.
This Review introduces tools to build transcriptional circuits and explains how the choice of different tools can affect circuit behavior and how its operation can be affected by the cellular host.
Raven calculates assembly plans for complex genetic constructs from thousands of parts. It integrates user feedback on failed intermediate assemblies to improve the final outcome.
Bioretrosynthesis is meant to simplify construction of metabolic pathways by screening only for the final desired product. This approach, aided by protein design and crystallography, is now used to synthesize an antiretroviral nucleoside analog and surprisingly identifies a new enzyme function.
Biofilms are multifunctional and environmentally responsive assemblies of living and non-living components. By using synthetic gene networks in engineered cells to regulate the production of extracellular amyloid fibrils, and by interfacing the fibrils with inorganic materials such as metal nanoparticles, stimuli-responsive synthetic biofilms with switchable functions and tunable composition and structure have now been produced.
Synthetic biology requires orthogonal inputs and outputs to avoid undesired crosstalk between genetic constructs. Transcription activator–like effectors (TALEs), which bind diverse DNA sequences and can thus be orthogonal, are now employed to construct NOR gates and logic circuits in mammalian cells.
Saccharomyces cerevisiae bearing engineered alginate and mannitol catabolic pathways can ferment sugars from brown macroalgae to produce ethanol, potentially allowing the use of brown macroalgae as a viable feedstock for the production of biofuels and renewable chemicals.
In synthetic biology designs, circuit components can generally move within the cell, meaning that functional cross-talk can cause faulty wiring. Genome mining, synthetic promoter construction and cross-reactivity screening now identify 20 orthogonal TetR repressor-promoter pairs for use in complex applications.
Designer gene circuits allow the controlled expression of proteins in response to specific stimuli. Here, Rössger et al.use synthetic biology approaches to create a fatty-acid biosensor that controls the production of a satiety hormone and use it to control diet-induced obesity in mice.
The problem of toxic intermediates in engineered metabolic pathways is mitigated by dynamic gene-expression regulation using stress-responsive promoters.
Cells can adapt rapidly to survive and efficiently exploit constantly changing environments by varying their mutation rate. Here the authors construct an in silicosystem to modulate mutation rate, and demonstrate that this method can be used in the laboratory to create specific phenotypes.
Synthetic transcription factors based on the RNA-guided CRISPR-Cas9 system are used to activate specific endogenous genes in human cells. Also online, Joung and colleagues report similar developments at two other loci.
For genetically engineered circuits, the movement of RNA polymerase across the DNA during transcription needs to be tightly controlled. A large library of strong terminators will make circuit design easier and more efficient.
Synthetic analog gene circuits can be engineered to execute logarithmically linear sensing, addition, ratiometric and power-law computations in living cells using just three transcription factors.
Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed.
By using a bicistronic design, with a leader peptide that overlaps with and contains the Shine-Dalgarno site for a downstream gene of interest, the authors demonstrate reliable, context-independent gene expression.
This linear ANOVA-based method quantifies the activity of different combinations of genetic elements and assigns a score that indicates the variation in performance across changing contexts.
Gene circuits created by synthetic biologists working in one system may not be functional when transferred to a different organism. Using computational modelling to identify factors underlying such differences, the authors successfully adapt a yeast ‘linearizer’ circuit so that it functions in mammalian cells.
Genome-wide variation in the directed evolution of metabolite-overproducing microbes requires high-throughput screening platforms. Yang et al.show that synthetic RNA devices can sense target metabolites, enrich pathway optimisation, and expedite the evolution of metabolite-producing microbes.
Microbial fatty acid-derived fuels represent promising alternatives to the traditionally used fossil fuels. Koffas and colleagues report that E. colicentral metabolism can be modified to produce large quantities of fatty acids through a modular pathway engineering strategy.
An efficient and scalable strategy with robust error correction is reported for encoding a record amount of information (including images, text and audio files) in DNA strands; a ‘DNA archive’ has been synthesized, shipped from the USA to Germany, sequenced and the information read.
Five experts discuss their views on the main achievements and challenges of synthetic biology in basic and applied science, consider potential ethical issues, and describe how synthetic biology relates to disciplines such as systems biology and computational modelling.
Engineering of gene circuits, DNA-binding domains and RNA regulators has led to a new generation of synthetic biology research tools, which enable the elucidation of gene function in mammalian cells. The possibility to rebuild complex signalling circuits outside of their normal context is also increasing our understanding of signalling pathways and is leading to innovative therapeutic interventions.
New tools for plant biotechnology are emerging, including synthetic promoters, 'tunable' transcription factors, genome-editing tools and site-specific recombinases. These tools promise to expand the range of plant biotechnology applications, especially when integrated with approaches for manipulating large DNA constructs.
Genetic code expansion for synthesis of proteins containing noncanonical amino acids is a rapidly growing field in synthetic biology. Creating optimal orthogonal translation systems will require re-engineering central components of the protein synthesis machinery on the basis of a solid mechanistic biochemical understanding of the synthetic process.
A bacterial enzyme that uses guide RNA molecules to target DNA for cleavage has been adopted as a programmable tool to site-specifically modify genomes of cells and organisms, from bacteria and human cells to whole zebrafish.
Progress in synthetic biology is facilitating the design and implementation of synthetic gene circuits. The parts and modules that must be combined in these systems and the barriers that must be overcome before more complex circuits are implemented are presented in this Review.