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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.

Synthetic RNA-based devices can dynamically control a wide range of processes. Here the authors develop a quantitative and high-throughput mammalian cell-based RNA-seq assay to efficiently engineer ribozyme switches.

Noscapine is a potential anticancer drug that is traditionally isolated from the opium poppy Papaver somniferum. Here, Li and Smolke reconstitute the noscapine gene cluster in Saccharomyces cerevisiae, to achieve the microbial production of noscapine and related pathway intermediates, and provide new insights into the biosynthesis of noscapine.

The alkaloid drugs hyoscyamine and scopolamine are synthesized from sugars and amino acids in yeast, using 26 genes from yeast, plants, bacteria and animals, protein engineering and a vacuole transporter to enable functional expression of a key acyltransferase.

The top down cheminformatics method is usually used for the reconstitution of heterologous pathway to produce plant natural products. Here, the authors report a bottom up computational workflow for the identification of potential products and the enzymes required to make them in a noscapine pathway in yeast.

Anti-CRISPR proteins derived from phage can abrogate CRISPR activity. The authors repurpose these molecules for demonstrating genomic write-protection and pre-programmed gene expression circuits.

Existing in vivo mutagenesis tools are limited by low mutation diversity and mutation rates. Here the authors present TRIDENT for targeted, continual and inducible diversification of genes of interest using deaminases fused to T7 RNA polymerase.

Biosensors are key to engineered biological systems. Here the authors demonstrate rapid de novo in vitro evolution of RNA biosensors of small molecules in a fully automated system.

Alternative splicing expands the genetic coding capacity and proteomic diversity of the cell. Here the authors create a synthetic biology platform for regulating four programmable exons in modular transcription factors.

Tropane alkaloids (TAs) are a group of phytochemicals that are used to treat neurological disorders. Here, the authors engineer baker’s yeast to produce tropine, a key intermediate in the biosynthetic pathway of TAs, and cinnamoyltropine, a non-canonical TA, from simple carbon and nitrogen sources.

A small set of promoters is used for most genetic construct design in S. cerevisiae. Here, the authors develop a predictive model of promoter activity trained on a data set of over one million sequences and use it to design large sets of high-activity promoters.

A model that incorporates the quantitative relationship between microRNA and the expression of its target gene achieves predictable and robust genetic circuits.

Screening for tertiary-interaction responsiveness in large RNA ribozyme-aptamer libraries to ligands identifies RNA devices with improved activation ratios and ligand sensitivities.

Metabolic engineering of yeast to incorporate plant and bacterial enzymes that construct and decorate morphine, along with spatial engineering to enable a spontaneous chemical reaction, provides strains capable of producing up to 130 mg/l of opioids.

Innovative community efforts in academia and non-profits to engage student researchers, encourage open sharing of DNA constructs and new methodology as well as build a Registry of Standardized Biological Parts have been central to the emergence of synthetic biology.

Engineering microbial cell factories for the production of useful plant natural products (PNPs) is a resource-conserving and environmentally-friendly synthesis route. Here, the authors review recent developments that enable engineering of hosts, pathways, and enzymes to make PNPs and PNP derivatives.

Synthetic RNA devices integrate sensing, processing and actuation of signals into defined, programmable functions to control cell behaviour. This Review discusses the emerging applications of RNA devices in biomedical research and biomanufacturing, as well as progress in creating new ligand sensors and new mechanisms of action with engineered RNAs.

Phytochemicals exhibit great pharmaceutical importance despite their low abundance in nature. The microbial biosynthesis of complex phytochemicals offers one route to increase their availability and production. This Review discusses recent strategies to reconstruct plant biosynthetic pathways that have not been fully elucidated; enhance plant enzyme activity; and enhance overall reaction efficiency of multi-enzyme pathways.

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.