Marine macroalgae, particularly their complex polysaccharides, are an untapped renewable source of high-quality monosaccharides and related building blocks. To utilize this feedstock for industrial applications, the enzymatic depolymerization by marine microorganisms has been shown to be effective. A prime example is the common green alga Ulva, with its storage polysaccharide ulvan, which contains high quantities of L-rhamnose and D-glucuronic acid. As suitable high-throughput methods for analyzing the enzymatic degradation of complex polysaccharides are still lacking, a transcription factor–based biosensor is described here that utilizes the PrhaBAD promoter native to E. coli, which is specific for L-rhamnose. This biosensor exhibited a linear response, enabling the quantification of L-rhamnose within a concentration range of 10–1000 µM. The introduction of a T7 stem-loop improved the performance, and various fluorescent reporter genes were studied. The optimized system was then used to evaluate various stages of the ulvan degradation cascade in terms of L-rhamnose release, confirming its applicability to complex sugar mixtures. A detectable fluorescence signal was only generated when all the necessary enzymes for breaking down the polymer into undecorated monosaccharides were present, highlighting the biosensor’s specificity. The application of this method to the degradation of Ulva sp. biomass samples of various origins was also successfully demonstrated. This establishes the biosensor as a promising method for further high-throughput investigations.

Phototrophic bacteria use solar energy to support metabolism and biochemical synthesis and are of increasing interest as systems for industrial chemical manufacture. Biosynthesis using phototrophic bacteria can use various renewable organic and inorganic carbon sources to drive chemical production, without an exogenous supply of refined organic carbon required for traditional dark fermentation used in industrial biotechnology. The potential to use solar energy to convert CO2 into useful products or upcycle diverse waste streams opens avenues for chemical manufacturing decoupled from fossil resource depletion, potentially with a smaller environmental footprint than other biotechnological routes. Despite this potential, the commercial application of phototrophic bacteria for this purpose is currently limited. In this Review, we discuss the basis for solar chemical bioprocesses in bacteria, emerging tools to engineer phototrophy for bioproduction and give examples of bulk chemical and high-value products synthesized in these species. Finally, we discuss the outlook for this nascent field in the context of chemical synthesis through engineering biology and outline the further progress required to realize the potential of light-powered microbial cell factories for future sustainable industrial synthesis. Phototrophic bacteria could be used for chemical manufacturing from various carbon sources. This Review discusses the pathways, engineering and potential application of solar chemical biosynthesis.

Whole-cell biosensors detecting the heavy metal arsenic have been widely studied for their potential in environmental monitoring. And while inducible biosensors have been shown to be an effective tool to tune the operational range, a thoroughly characterized inducible biosensor is currently lacking. Here, we present an E. coli biosensor for arsenic in which the transcription factor (TF) gene arsR is inducible by naringenin, a plant-derived secondary metabolite. Increasing the naringenin concentration reduced the basal output while increasing both the dynamic range and sensing threshold of the biosensor dose-response curve, but the operational range appeared constrained by a fixed upper limit. Comparison with a previously published phenomenological model revealed good overall agreement between experimental data and model predictions, except for the behavior of the maximum output and threshold. This work expands the biosensor toolbox with a profoundly characterized arsenic biosensor and raises a potential practical limit to dose-response curve engineering by tuning TF expression alone.

In the ongoing arms race with phages, bacteria have evolved diverse defense systems, such as CRISPR–Cas and restriction–modification systems. The DNA double-strand break repair system represents a core mechanism for maintaining genomic integrity and is vital for cell survival. However, it remains unknown whether and how these repair systems contribute to phage resistance. This study systematically investigates the role of the non-homologous end joining (NHEJ) during phage infection in Mycobacterium smegmatis. We found that NHEJ deficiency compromises host resistance to phage SWU1, as evidenced by increased plaque counts and reduced bacterial survival. Mechanistically, phages exploit host NHEJ for genomic repair; however, the error-prone nature of NHEJ leads to imperfect repair at phage cos sites, thereby blocking replication. The host modulates the balance between NHEJ and homologous recombination (HR) to control repair fidelity: NHEJ loss shifts the balance toward high-fidelity HR, which in turn promotes phage survival. Furthermore, NHEJ deficiency exacerbates infection-induced oxidative stress, leading to a compromise in bacterial viability. Our findings reveal the multifaceted functions of NHEJ in mycobacterium–phage interactions and provide new insights into how DNA repair systems shape antiphage defense and coevolution.

Cooperative interactions within large protein assemblies are crucial for cellular information processing. However, direct observations of cooperative transitions have been limited to compact molecular assemblies. Here we report the in vivo measurements of spontaneous discrete-level transitions in the activity of an entire E. coli chemosensory array—an extensive membrane-associated assembly comprising thousands of molecules. Finite-size scaling analysis of the temporal statistics reveals nearest-neighbor coupling strengths within 3% of the Ising phase transition, indicating that chemosensory arrays are poised at criticality. We also show how E. coli exploits both static and dynamic disorder, arising from chemoreceptor mixing and sensory adaptation, respectively, to temper the near-critical dynamics. This tempering eliminates detrimental slowing of response while retaining substantial signal gain as well as an ability to modulate physiologically relevant signal noise. These results identify near-critical cooperativity as a design principle for balancing the inherent trade-off between response amplitude and response speed in higher-order signalling assemblies. Many biological systems appear to organize their dynamics close to a critical point. Now it is shown that the protein array mediating Escherichia coli chemosensing is near-critical, enabling large signal amplification without compromising response speeds.

Engineered bacteria are emerging as a transformative class of cancer therapeutics. Recent advances in synthetic biology have expanded the genetic circuit toolbox, enabling the programmable control of attenuation, payload release, and immunomodulation. These developments have transformed bacteria from simple, colonizing agents into a versatile chassis for complex therapeutic functions. In this review, we examine recent circuit-based strategies for enhancing tumor specificity, regulating therapeutic delivery and engaging the host immune system, with emphasis on programming spatiotemporal control and consortia behavior. We consider current barriers to clinical translational and discuss how rational engineering can guide the next generation of microbial therapeutics.

Ribosomes are central to protein synthesis in all organisms. In mammals, the ribosome functional core is highly conserved. Remarkably, two rodent species, the naked mole-rat (NMR) and tuco-tuco, display fragmented 28S ribosomal RNA (rRNA), coupled with high translational fidelity and long lifespan. The unusual ribosomal architecture in the NMR and tuco-tuco has been speculated to be linked to high translational fidelity. Here, we show, by single-particle cryo-electron microscopy, that despite the fragmentation of their rRNA, NMR and tuco-tuco ribosomes retain their core functional architecture. Compared to ribosomes of the guinea pig, a phylogenetically related rodent without 28S rRNA fragmentation, ribosomes of NMR and tuco-tuco exhibit poorly resolved density for certain expansion segments. In contrast, the structure of the guinea pig ribosome shows high similarity to the human ribosome. Enhanced translational fidelity in the NMR and tuco-tuco may stem from subtle, allosteric effects in dynamics, linked to rRNA fragmentation.

As DNA sequencing technologies improve, it is becoming easier to sequence and assemble new genomes from non-model organisms. However, before a newly assembled genome sequence can be used as a reference, it must be annotated with genes and other features. This can be conducted by individual laboratories using publicly available software. Modern genome annotations integrate gene predictions from the assembled DNA sequence with gene homology information from other high-quality reference genomes and take into account functional evidence (e.g., protein sequences and RNA sequencing information). Many genome annotation pipelines exist but have varying accuracies, resource requirements and ease of use. This genome annotation Tutorial describes a streamlined genome annotation pipeline that can create high-quality genome annotations for animals in the laboratory. Our workflow integrates existing state-of-the-art genome annotation tools capable of annotating protein-coding and non-coding RNA genes. This Tutorial also guides the user on assigning gene symbols and annotating repeat regions. Finally, we describe additional tools to assess annotation quality and combine and format the results. This Tutorial integrates state-of-the-art tools into a streamlined workflow to create high-quality annotations for animal genomes, assigning gene symbols and annotating repeat regions for both protein-coding and non-coding RNA genes, before assessing annotation quality.