Plant-based materials provide a renewable and sustainable platform for tackling global challenges in energy, environment and healthcare. Among these, chronic diabetic wounds, currently affecting over 10% of the global population, remain a pressing public health crisis, largely owing to persistent hypoxia and unresolved inflammation. Here we report photosynthetic microspheres derived from the invasive aquatic plant Eichhornia crassipes (water hyacinth) as a green therapeutic strategy for chronic wound repair. Harnessing intact chloroplasts, these biogenic microspheres deliver sustained oxygen evolution for up to 3 weeks, alleviating local hypoxia and restoring redox balance. When integrated with the metabolic regulator metformin, the system couples exogenous photosynthesis and endogenous glucose metabolism, synergistically reprogramming the wound microenvironment. In both mouse and pig diabetic wound models, this approach suppresses inflammation, promotes angiogenesis and expedites re-epithelialization, leading to adaptive tissue regeneration. Our findings reveal that inexpensive, invasive aquatic biomass can be upcycled into advanced therapeutic biomaterials, offering a scalable and sustainable framework for next-generation regenerative medicine. This study showcases the upcycling of invasive water hyacinth into photosynthetic microspheres which provide sustained oxygen evolution and metabolic regulation, significantly accelerating the healing process of chronic diabetic wounds.

GDP-Mannose transporters are Golgi-localized solute carriers that are essential for the virulence of pathogenic fungi, serving as critical components of fungal glycosylation pathways. However, the mechanism by which nucleotide sugars are recognised and transported across the Golgi membrane remains unclear, hindering efforts to develop effective inhibitors that could serve as distinct antifungal agents. Here, we present cryo-EM structures of the GDP-Mannose transporter, Vrg4, from Candida albicans in complex with nanobodies in both the cytoplasmic and Golgi-facing states. Structural comparisons between these two states, in addition to a GDP-mannose bound structure, demonstrate the importance of ligand movement during transport. Additionally, we demonstrate the ability of the nanobodies to specifically inhibit Vrg4, presenting proof-of-principle that nanobodies can be used as effective inhibitors of nucleotide sugar transport and glycosylation in cells. Invasive fungal pathogens have become a significant concern in healthcare systems worldwide. Here, authors demonstrate that nanobodies targeting the GDPmannose transporter can arrest fungal cell growth. The structures also reveal the complete transport cycle for an SLC35 nucleotide sugar transporter.

Water environments serve as critical sources and conduits for antimicrobial resistance (AMR). The complex water cycle facilitates the transmission of antibiotics, resistant bacteria and resistance genes that have been released through anthropogenic activities, thereby reshaping AMR dynamics across different environmental compartments. Among these resistance determinants, inactivating antibiotic resistance genes (inactivating ARGs) encode enzymes that degrade or modify antibiotics to reduce their bioactivity. They play a complex and dual role bridging environmental reservoirs and clinical risk. While they can threaten the therapeutic effectiveness of antibiotics when transferred horizontally to pathogens, they also act as cooperative traits that lower local concentrations of bioactive antibiotics and relax selection for resistance. In turn, reduced antibiotic exposure can enhance ecosystem functions and stability in both host-associated and environmental microbiomes through ecosystem resilience and community protection. Inactivating ARGs represent a crucial intersection between AMR challenges and microbial community stability. Here we discuss the risks and ecological benefits of inactivating ARGs, and present intervention strategies aiming to both protect ecological resilience and limit resistance development in pathogens. Water environments are pivotal in the spread of antimicrobial resistance, acting as conduits for antibiotics and resistance genes. Here, the authors explore the dual role of inactivating antibiotic resistance genes, highlighting their ecological benefits and risks, and propose strategies to enhance ecosystem resilience while curbing resistance in pathogens.

The systematic exploration of novel bioactive compounds with superior functional properties is critical for driving innovations in agriculture, healthcare, and related fields, thereby becoming essential for advancing sustainable biotechnological solutions. Nonprotein amino acids (NPAAs), functional amino acids not incorporated into proteins, exhibit unique physiological activities and provide distinctive advantages in nutritional enhancement, functional product formulation, and food/feed processing. These attributes challenge the conventional perception of proteins as mere nutritional carriers, positioning NPAAs as promising bioproducts for biosynthesis and functional applications in agriculture, food, and medicine. This review summarizes the classification of the available NPAAs based on their synthetic substrates for the first time and then outlines their diverse functional roles. A comprehensive analysis of recent advances in biosynthetic pathways, engineering strategies, and production level demonstrates their primary research progress in the laboratory phase. The further sustainable biomanufacturing of NPAAs is hampered by several challenges, including poorly elucidated biosynthetic mechanisms, limited robustness and low productivity of microbial strains, and difficulties in scaling up production for industrial applications. Addressing these bottlenecks will require innovative strategies and technologies to facilitate the translation of NPAA production from bench to industry. This review offers valuable insights into the potential of NPAAs in the development of next-generation bioproducts of nutrition, immune regulation, antioxidant defense, and intestinal homeostasis maintenance, suggesting a promising direction for microbial production of high-performance bioactive molecules in agricultural synthetic biomanufacturing.

CRISPR–Cas effectors typically rely on RNA guides to recognize target sequences. In Cas12a, the protospacer adjacent motif on DNA engages conserved protein residues, triggering target binding and nuclease activation. Here we reprogram Cas12a into a DNA-guided, RNA-targeting effector. Exploiting protospacer-adjacent motif-dependent interaction, we engineer synthetic CRISPR DNA that engages Cas12a to form a functional deoxyribonucleoprotein complex, while repurposing solely RNA as the programmable target. Structural, biophysical and biochemical analyses reveal the molecular basis of this DNA-guided, RNA-targeting configuration and support an activation pathway distinct from that of canonical RNA-guided systems. DNA-guided Cas12a enables direct RNA detection and efficient intracellular RNA knockdown, establishing a modular activation architecture for CRISPR–Cas12a and expanding the design space for programmable RNA manipulation. Synthetic DNA guides (crDNA) reprogram Cas12a nucleases for RNA targeting.

Cytoplasmic abundant heat-soluble (CAHS) proteins, a stress-responsive intrinsically disordered protein from tardigrades, have been discovered to form gel-like networks providing structural support during dehydration, thus enabling anhydrobiosis. However, the mechanism by which CAHS proteins protect the dehydrating cellular membrane remains enigmatic. Using giant unilamellar vesicles (GUVs) as a model membrane system, here we show that encapsulated CAHS12 undergoes a reversible structural transformation that reinforces membrane integrity and preserves encapsulated components, mimicking natural anhydrobiosis. CAHS12-containing GUVs demonstrated stability for weeks and mechanical robustness under dehydration, elevated temperature, and osmotic stresses. Molecular simulations suggest that CAHS12 forms a filamentous network within the vesicle lumen that mitigates membrane collapse and preserves compartmental architecture. Synthetic cells with cell-free transcription-translation capabilities withstand desiccation and recover biochemical activities, akin to the tun state of the tardigrade. This discovery opens up synthetic cell applications in bioengineering, cold-chain-independent biomanufacturing, and adaptive biointerfaces. Synthetic cells with tardigrade protein CAHS12 mimic desiccation survival by stabilizing membranes. This study uncovers how CAHS12 preserves cell structure and suggests new applications in biomanufacturing and adaptive biointerfaces.

Directed evolution methods face trade-offs between the control of discrete approaches and the throughput of modern continuous systems. Here, we engineered a method called lytic selection and evolution (LySE) for near-continuous evolution of bacterial gene clusters while maintaining discrete checkpoints. We developed a hypermutagenic T7 DNA polymerase variant fused to a dual adenine-cytosine deaminase to install all possible transition mutations at similar frequencies. By relieving pressure from maintaining genome fidelity, we obtained mutation rates of 3.82 × 10−5 substitutions per base. For biocontainment, the T7 DNA polymerase was encoded on an accessory plasmid, while the target gene cluster was encoded on a T7 DNA polymerase-lacking T7 phagemid. Alternating cycles of lysis and transduction enable selective replication and mutagenesis of target genes, while off-target genomic mutations are discarded. LySE evolved a 25-fold increase in tetA-encoded tigecycline resistance in 5 cycles, and a 50.9% increase in endpoint biomass of a bacterial strain that uses the polyethylene terephthalate monomer, ethylene glycol, as its sole carbon source. Our method balances speed and control for directed bacterial evolution. The lytic selection and evolution (LySE) system uses a plasmid-encoded, hypermutagenic T7 DNA polymerase and T7 phagemid-encoded target genes to enable controllable, near-continuous directed evolution of large gene clusters.

Phenotypic heterogeneity, a feature of both bacteria and eukaryotic cells, arises from inherent cell-to-cell variability. In eukaryotes, single-cell RNA sequencing has led to an explosion in understanding how heterogeneity impacts different cell types and states in organs and tissues. While single-cell RNA sequencing analyses in bacteria have lagged behind eukaryotic studies, recent technological advances now enable similar, high-resolution studies to be performed at scale in bacteria, yielding fundamental insights into how heterogeneity influences bacterial physiology, metabolism, antibiotic resistance, pathogenesis and interactions within complex microbial communities. Here we review recent advances in bacterial single-cell RNA sequencing, including the methods developed so far and what has been learned from their application. We also discuss technological and computational challenges going forwards, the need for standardization and how that could be achieved, and how this emerging field is now poised to revolutionize our understanding of bacterial physiology, infection biology and interactions within bacterial communities, such as the microbiota. This Review summarizes recent advances in bacterial single-cell transcriptomics approaches, while also discussing technological and computational challenges remaining to be met and the need for standardization going forwards.