Polymer design is being reshaped by demands for low-carbon fabrication and bioactive/living function. We trace the bidirectional interface between microbes and polymers. First, we analyze how microbes synthesize polymers like polysaccharides, polyesters, and proteins and how post-synthesis processing (via mechanical and/or chemical treatments) reshapes molecular architecture and mechanical and thermal properties. We compare reported properties, highlight missing metrics, and evaluate sustainability levers including solvent recovery, cradle-to-gate impacts, and biodegradation/biocontainment constraints. Second, we examine how polymers shape the behavior of living organisms in the context of engineered living materials. Design is organized around four axes—regulating adhesion and detachment, sustaining or directing growth for regeneration, imposing spatial organization on consortia, and tuning phenotype—with implementations in drug delivery, carbon capture, antimicrobial screening, and structural composites. Finally, we outline how automation, artificial intelligence–guided experimentation, and robust sustainability metrics can couple performance with responsible deployment.

A long-standing goal in biomedical research is to label and manipulate intracellular targets, which could be achieved through the cytosolic delivery of exogenous functional proteins. The development of Tat clusters has advanced the nontoxic intracellular delivery of functional antibodies at low concentrations, but the variety of proteins that can be successfully delivered remains limited. Here, we find that by simply reversibly modifying the surface of functional proteins with anionic peptide patches, various protein cargoes (which are normally difficult to deliver) can be delivered into living cells by synergetic electrostatic interactions with the cationic cell-penetrating peptide clusters TAT3. To demonstrate the applicability of this approach, we successfully deliver functional proteins with widely varying molecular weights (∼1.5 kDa to 430 kDa) and isoelectric points (less than 5 to greater than 9) into the cytosol of cells. By exploiting this method, we also achieve protein delivery in plant tissues, which is more challenging due to the presence of intact plant cell walls. This strategy is further applied for the cytosolic delivery of synthetic protein probes carrying posttranslational modifications (PTMs), which can aid in in situ mapping of the intracellular PTM-mediated interactome. Overall, this strategy is expected to enrich cytosolic protein delivery technology and help to repurpose a wide range of customized and therapeutic proteins for emerging intracellular applications. The development of Tat clusters has advanced the intracellular delivery of functional antibodies at low concentrations, but the variety of proteins that can be successfully delivered remains limited. Here, the authors report that by reversibly modifying the surface of functional proteins with anionic peptides, various protein cargoes (otherwise difficult to deliver) can be delivered into living cells by synergetic electrostatic interactions with the cationic cell-penetrating peptide clusters TAT3.

Coral reefs are one of the most biodiverse and productive ecosystems on Earth. However, corals are currently under threat from increasing ocean temperatures driven by climate change. Despite the known importance of these fragile ecosystems, our understanding of the molecular mechanisms driving ecologically important traits has been constrained by a lack of genetic tools for functional characterization. To address this limitation, we have developed straightforward and efficient methods to genetically modify corals and study gene function throughout various life history stages using CRISPR–Cas9-based mutagenesis. In this protocol, we first describe how to spawn and collect gametes from the coral Acropora millepora during seasonal spawning events. Next, we describe a method for microinjection of one-cell coral zygotes with CRISPR–Cas9 reagents. We include considerations about effective single-guide RNA design, methods for identifying successfully injected animals, strategies for rearing mutant larvae and juveniles, and methods for the detection and quantification of genomic modifications. This protocol is currently the only way to perform gene editing in corals and takes ~2–4 weeks to complete and has been successfully applied to study genes controlling heat tolerance in coral larvae and skeleton formation in coral juveniles. These technical advances set the foundation for a new field using reverse genetics to study ecologically important traits in corals, such as the establishment of symbiosis and its breakdown upon heat stress. In this protocol, the authors present straightforward and efficient methods to genetically modify corals and study gene function throughout various life-history stages using CRISPR–Cas9-based mutagenesis.

Biological upcycling is a promising strategy for handling end-of-life plastics. However, current practices, which predominantly focus on yielding fixed single outputs, face challenges in meeting diverse and evolving product demands. Here we present a programmable microbial assembly line that enables the efficient and versatile upcycling of plastic waste into various end products. The assembly line involves a deconstruction strain that catabolizes pretreated polyethylene terephthalate into pyruvate, serving as a universal building block, and a set of interchangeable production strains that transform this building block into tailorable outputs. Such a design allows a rapid, combinatorial assembly of microbial strains into diverse biomanufacturing systems. Accordingly, programmable upcycling is achieved, yielding successful production of a wide range of final products, including chemicals, fuels, enzymes, biopolymers and electricity. This work establishes a reconfigurable valorization platform, providing insights into biological treatment of plastic waste as well as into need-driven, sustainable biomanufacturing. Strategies to upcycle plastic waste are critically needed to mitigate their impacts on the environment and public health. Here the authors introduce a programmable, microbial-based platform that converts end-of-life plastics into a suite of high-value products, ranging from fuels to biopolymers.

L-lysine (Lys) has been explored as a potential cyanobactericide due to its inhibitory effects on cyanobacterial growth at micromolar concentrations, comparable to many antibiotics. Here, we investigated the early metabolic and physiological responses of the model cyanobacterium Synechocystis sp. PCC 6803 to Lys exposure. Physiological analyses revealed cell enlargement, oxidative stress, and photosynthesis inhibition, leading to growth arrest. Metabolomic profiling indicated disruptions in peptidoglycan biosynthesis, evidenced by the accumulation of L-/D-alanine, meso-diaminopimelate, and D-Ala-D-Ala, suggesting interference with cell wall integrity. Furthermore, levels of energy metabolites and other amino acids, including tyrosine, tryptophan, valine, and iso-/leucine, were significantly altered, implying broader metabolic impacts of Lys toxicity. To explore potential resistance mechanisms, we used a CRISPRi-based genetic screen to identify key genes involved in relieving Lys toxicity. The Bgt permease system, responsible for basic amino acid uptake, was essential for acquiring Lys resistance, as a bgtA mutant exhibited normal growth on elevated Lys concentrations, thereby validating our CRISPRi screen. Additionally, UirR, a DNA-binding response regulator, and genes linked to c-di-AMP signaling, seemed implicated in Lys metabolism. Deletion of the c-di-AMP synthase gene increased Lys sensitivity, supporting a role for c-di-AMP in cell wall homeostasis and osmotic stress regulation. Altogether, our findings explored the early metabolic responses and physiological consequences of Lys exposure in Synechocystis, demonstrating its effects on peptidoglycan biosynthesis, amino acid metabolism, and nucleotide biosynthesis. This, as well as the identification of key genetic factors contributing to Lys resistance, provides insights into cyanobacterial physiology and the potential application of Lys in bloom-control strategies.

Pathogenic bacteria rely on the stringent response to adapt to hostile environments encountered within the host. However, the mechanisms by which host-induced stress activates this response remain poorly understood. Here, we identify iron-sulfur (Fe-S) cluster damage as a conserved trigger of the stringent response in major Gram-negative pathogens, including Salmonella enterica, Enterobacter cloacae, and Klebsiella pneumoniae. We demonstrate that Fe-S cluster disruption—triggered by oxidative stress or metal imbalance—limits intracellular pools of sulfur-containing and branched-chain amino acids, thereby activating the (p)ppGpp synthetase RelA. We further show that during Fe-S cluster stress, (p)ppGpp plays a dual role: enhancing bacterial fitness and promoting virulence by upregulating the Salmonella SPI-2 type III secretion system T3SS. These findings reveal a conserved mechanism by which pathogenic bacteria integrate host-associated stresses into an adaptive transcriptional response that promotes fitness and virulence, highlighting Fe-S cluster integrity as a central hub for environmental sensing during infection. Pathogenic bacteria rely on the stringent response to adapt to environments within the host. Here, Michaud et al. show that iron-sulfur cluster damage acts as a conserved signal that triggers the stringent response.

The differences in response times between vegetation physiology and vegetation structure to water stress at the global scale remain unclear. Here, we integrate solar-induced chlorophyll fluorescence satellite observations, optical remote sensing indices, and hydrometeorological data to globally disentangle the sequence and related factors of vegetation physiological and structural responses to drought. We isolated fluorescence efficiency by normalizing solar-induced chlorophyll fluorescence by absorbed photosynthetically active radiation; We show that fluorescence efficiency is a robust proxy for ecosystem-level vegetation physiology and responds to drought within ~3 days, while structural changes emerge after ~12 days. The contrast in timing is clearest in humid regions, owing to the sustained soil moisture availability during the initial stage of drought. Physiological responses are more temporally aligned with changes in vapor pressure deficit, whereas structural changes coincide more with soil moisture dynamics, reflecting differing patterns of association under increasing drought stress. These findings advance mechanistic understanding of vegetation drought responses across the continuum from physiological to structural processes. Satellite solar-induced fluorescence uncovers subtle leaf processes. This study suggests that it reveals rapid drought responses that precede structural changes and are not captured by other satellite products, showcasing its value for ecosystem and climate research.

The pandemic-scale progression of type 2 diabetes mellitus (T2DM) necessitates innovative interventions targeting the pathogenic triad of insulin resistance, dysregulation of lipid metabolism, and gut microbiome dysbiosis. Here, we report a synthetically bioengineered probiotic consortium (REcN-F/Ca) developed through directed metabolic adaptations of E. coli Nissle 1917 (EcN) under iterative hydrogen peroxide selection, subsequently functionalized with fructooligosaccharide-calcium carbonate composites. REcN-F/Ca exhibits enhanced reactive oxygen species tolerance through upregulated antioxidant enzymes and hydrogen sulfide-mediated redox balancing, alongside improved gastrointestinal survivability. In high-fat diet-induced obese male mice, REcN-F/Ca restores gut microbiota diversity, enriches butyrogenic taxa (Lachnospiraceae and Blautia), and rescues short-chain fatty acids depletion. Transcriptomic profiling reveals PPAR signaling activation, driving lipid metabolism and suppressing adipose inflammation. These effects translate to systemic metabolic improvements with attenuated weight gain (−25.4%), restored glucose homeostasis, and reduced insulin resistance (HOMA-IR: −73.2%) in the obesity and T2DM murine model. Our findings establish REcN-F/Ca as a synthetically engineered probiotic that simultaneously corrects intestinal ecological perturbations and reverses host metabolic dysfunction, proposing a paradigm for metabolic syndrome management. Novel treatments are needed for type 2 diabetes mellitus which target insulin resistance, lipid metabolism dysregulation, and gut microbiome dysbiosis. Here the authors engineered a probiotic to tolerate oxidative stress, an alleviate type 2 diabetes in mice by activating host metabolic pathways.

Microbial consortia hold immense promise for wastewater treatment by harnessing metabolite exchange-based interspecies interactions to drive energy and matter flow. Yet, challenges in the coordinated modulation of transmembrane transport proteins and extracellular metabolite distribution limit cross-species interactions within consortia. Here we propose a mesospace-domain regulation strategy that leverages hydrogel-assembled mesoscale habitats to precisely modulate β-barrel membrane porins and locally enrich cross-fed molecules, thus remodelling interspecific cooperative metabolism for efficient wastewater treatment. Confining a carefully designed microbiota within mesospace enhances organic wastewater treatment for hexanoate production, achieving a 307.2% higher yield than unconfined systems. This improvement is attributed to mesospace-governed porin regulation and exometabolite enrichment, which reprogram interbacterial interactions from unidirectional electron transfer to bidirectional multimetabolite cross-feeding. This regulatory strategy is also applicable to other wastewater treatment systems, markedly enhancing succinic acid production, denitrification of low carbon-to-nitrogen ratio wastewater and removal of emerging contaminants. These findings illuminate how the mesospace domain orchestrates microbiota metabolism to boost bioconversion efficiency and selectivity for sustainable wastewater management. Microbial consortia offer a promising route for sustainable wastewater treatment but are often constrained by inefficient interspecies metabolic interactions. This study shows that hydrogel-defined mesospace confinement enhances interspecies cross-feeding by regulating transmembrane transport and metabolite retention, improving pathway selectivity and treatment efficiency.