Molecular engineering articles within Nature Communications

Methylotrophic metabolism enables growth on methanol, an alternative to sugar fermentation. Here the authors use adaptive laboratory evolution to uncover native methylotrophy capacity in Saccharomyces cerevisiae.

Molecular tagging using DNA is an attractive option in cases that are not suitable for RFID tags or QR codes. Here, the authors present Porcupine, DNA tags directly classifiable from raw nanopore signals.

Gene drives may be impeded by the generation of resistant alleles following NHEJ. Here the authors develop a recoded gene-drive rescue system for the malaria mosquito, Anopheles stephensi, that targets the drive to the kynurenine hydroxylase gene for negative selection against mutated alleles.

Measuring interaction energies from experimentally measured single-molecular interactions is challenging. Here, the authors report a gamma work distribution applied to single molecule pulling events for estimating peptide absorption free energy.

A challenge for biological chemical production is the completion between synthetic circuits and host resources. Here the authors the authors use quorum sensing circuits and global mRNA decay to independently control two phenotypic states.

Synthetic biology logic gates can be used to distinguish healthy cells from cancer cells. Here the authors design minigene circuits that show more robust identification of cancer cells compared to traditional genetic circuits.

Non-antibiotic selection systems could also serve as biocontainment strategies. Here the authors present a fluoride sensitivity selection system for use in yeast.

The design of nucleic acid hybridisation probes is important for their use in DNA nanotechnology and biomedical applications. Here the authors use a DNA equalizer gate approach that expands the detection windows for improved sequence selectivity.

The extreme oxygen sensitive character of hydrogenases is a longstanding issue for hydrogen production in bacteria. Here, the authors build carboxysome shells in E. coli and incorporate catalytically active hydrogenases and functional partners within the empty shell for the production of hydrogen.

The current bottleneck for DNA data storage systems is the cost and speed of synthesis. Here, the authors use inexpensive, massively parallel light-directed synthesis and correct for a high error rate with a pipeline of encoding and reconstruction algorithms.

Expansion of the chemical diversity of glycopeptide antibiotics (GPAs) to deal with the emergence and spread of GPA resistance is challenging. Here, the authors report a GPA synthetic biology platform in Streptomyces coelicolor for Type IV–V glycopeptide antibiotic production and discovery.

ADP-ribose binding macro domains facilitate the enrichment and detection of cellular ADP-ribosylation. Here, the authors generate an engineered macro domain with increased ADP-ribose affinity, improving the identification of ADP-ribosylated proteins by proteomics, western blot and immunofluorescence.

Synthetic biology is among the most hyped research topics this century, and in 2010 it entered its teenage years. But rather than these being a problematic time, we’ve seen synthetic biology blossom and deliver many new technologies and landmark achievements.

Cellular optogenetics applications are limited by difficulties in quantification and blue light toxicity. Here the authors design LOV2-based switches that use resonance energy transfer to overcome these concerns.

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunomodulatory receptors expressed on cells of the hematopoietic lineage. Here the authors demonstrate an approach for the identification of the glycan ligands of Siglecs, which is also applicable to other families of glycan-binding proteins.

RNA can be used as a programmable tool for detection of biological analytes. Here the authors use deep neural networks to predict toehold switch functionality in synthetic biology applications.

The chemical stability of DNA makes complete erasure of DNA-encoded data difficult. Here the authors mix true and false messages, differentiated by whether a truth marker oligo is bound to it, and show that brief exposure to elevated temperatures randomizes the binding of truth markers preventing data recovery.

In contrast to genetic circuits, here the authors develop protein biocircuits based on proteases. They show these activity-based circuits can execute Boolean logic for programmable drug delivery and perform fuzzy logic to solve a mathematical oracle problem, Learning Parity with Noise.

CRISPR-Cas12a based detection systems can be sensitive down to the picomolar range. Here the authors modify the 3′- and 5′-ends of the crRNA and show this enhances trans-cleavage for improved sensitivity.

Current gene drive strategies are restricted to sexually reproducing species. Here the authors develop a gene drive in herpesviruses that allows the spread of an engineered trait through a viral population.

Synthetic Biology often lacks the predictive power needed for efficient bioengineering. Here the authors present ART, a machine learning and probabilistic predictive tool to guide synthetic biology design in a systematic fashion.

Short hairpin RNAs can be used to modulate and regulate gene expression. Here the authors generate chimeric RNAs that interact with the photoreceptor PAL, allowing for optoribogenetic control of cell physiology.

The mechanisms for regulating translation re-initiation in bacteria remain poorly understood. Here, the authors screened a library of synthetic operons and identified a ribosome termination structure that modulates re-initiation efficiency and which is conserved across bacteria.

Automated frameworks to systematically implement robust history-dependent genetic programs in cellular populations.

Non-ribosomal peptide synthases are multimodular enzymes comprised of adenylation (A), condensation (C) and thiolation domains. Here, the authors show that non-ribosomal peptides can be generated solely by A domain substitutions, providing evidence that the postulated substrate specifying role of C-domains may be rare in nature.

The SARS-CoV-2 pandemic has created large demand on global testing capability. Here the authors use the London Biofoundry, an automated synthetic biology platform, and develop an open-source virus-like particle to implement high-throughput diagnostics.

Natural speciation can be driven by pre-zygotic and post-zygotic barriers. Here the authors use a dominant lethal transgene coupled to a recessive resistance allele to engineer species-like barriers in Drosophila.

Transcriptional anti-repressors have been largely absent in the design of regulated genetic circuits. Here, the authors present a workflow of the engineering of non-natural anti-reperssors that can be built into NOT oriented logic gates.

Self-propagating drives allow for non-Mendelian inheritance. Here the authors use CRISPR to build a chromosome drive, showing elimination of entire chromosomes, endoreduplication of desired chromosomes and enabling preferential transmissions of complex genetic traits on a chromosomal scale in yeast.

Backbone extended monomers are poorly compatible with the natural ribosomes, impeding their polymerization into polypeptides. Here the authors design non-canonical amino acid analogs with cyclic structures or extended carbon chains and used an engineered ribosome to improve tRNA-charging and incorporation into peptides.

A cell free or synthetic biochemistry approach offers a way to circumvent the many constraints of living cells. Here, the authors demonstrate, via enzyme and process enhancements, the production of isobutanol with the metrics exceeding highly developed ethanol fermentation.

Intercellular signalling is fundamental for the formation of complex structures from single cells. Here the authors design six orthogonal cell–cell signalling channels for cell consortia communication and bio-computation.

Regulatory networks respond to environmental and genetic perturbations by reprogramming metabolism. Here the authors screen a library of 82 regulators with 110,120 mutations to map the regulatory network of 4000 genes.

The ability to reversibly control monobody binding affinity would find use in biotechnology and research applications. Here the authors fuse the light-sensitive AsLOV2 domain to a monobody against the Abl SH2 domain to obtain a light dependent monobody and apply it in vitro and in mammalian cells.

Cas9 fusions partners are often limited to natural polypeptide chains at the Cas9 termni. Here the authors present a platform for site-specific and multiple-site conjugation to both termini and internal sites of Cas9, and they apply this platform to efficiently engineer insulin-producing β cells.

The ability to regulate nanobody affinity with light would expand the applications toolbox for these reagents. Here the authors insert an optimised photoswitchable AsLOV2 domain into multiple nanobodies and demonstrate photoswitchable binding to fluorescent proteins and endogenous proteins in cells.

Anhydrotetracycline and tetracycline are commonly used chemicals to regulate transcription and translation, respectively. Here the authors exploit the natural photosensitivity of these molecules to place their activity under optical control.

Current light-inducible Cre-loxP systems have minimal capacity for deep tissue penetration. Here, the authors present a far-red light-induced split Cre-loxP system for in vivo genome engineering.

Insertions/Deletions (InDels) remain an untapped source of protein diversity in laboratory evolution. The method TRIAD generates libraries of random variants with short in-frame InDels using transposons, allowing a comparison of their evolutionary potential with widely-used point mutant libraries.

Genetically encoded voltage indicators (GEVIs) allow visualisation of fast action potentials in neurons but most are bright at rest and dimmer during an action potential. Here, the authors engineer electrochromic FRET GEVIs with fast, bright and positive-going fluorescence signals for in vivo imaging.

DNA is an attractive digital data storing medium due to high information density and longevity. Here the authors use millions of sequences to investigate inherent biases in DNA synthesis and PCR amplification.

Orthogonal aminoacyl-tRNA synthetase/tRNA pairs are crucial for the incorporation of unnatural amino acids in a site-specific manner. Here the authors use rational chimera design to create multiple efficient pairs that function in bacterial and mammalian systems for genetic code expansion.

Class 1 type I CRISPR–Cas systems have not been as extensively developed for genome engineering as Class 2 systems. Here the authors modify the Type I–F CRISPR–Cas system for transcriptional activation of gene expression.

Synthetic biological modules can be used to reprogram host proteomes, which in turn enhance the function of the synthetic modules. The authors use this holistic synthetic biology approach to engineer a more favorable environment for cell-free protein synthesis.

Insect population control using conditional lethal systems could break down due to spontaneous mutations that render the system ineffective. Here the authors analyse the structure and frequency of such mutations in Drosophila and suggest the use of dual lethality systems to mitigate their survival.

Control over splicing could be used for both therapeutic and engineering applications. Here the authors create artificial splicing factors using RNA-targeting CRISPR systems under small molecule control.

The physical architectures of information storage dictate how data is encoded, organised and accessed. Here the authors use DNA with a single-strand overhang as a physical address to access specific data and do in-storage file operations in a scalable and reusuable manner.

Previous design strategies for pH sensitive aptamers were not readily tunable across pH ranges. Here the authors present a general method to convert aptamers into pH-responsive switches using two orthogonal motifs.

Some human amyloid proteins have been shown to interact with viral proteins, suggesting that they may have potential as therapeutic agents. Here the authors design synthetic amyloids specific for influenza A and Zika virus proteins, respectively, and show that they can inhibit viral replication.