Solar-driven biosynthesis from carbon dioxide can facilitate sustainable chemical manufacturing. However, cell-density limits and contamination susceptibility have seriously hampered its practical implementation. Here we develop a solar–chemical hybrid-driven biosynthesis (SCHB) strategy integrating wastewater-based phosphorus recovery into biological photosynthetic metabolism for chemical production. Specifically, we incorporate the phosphite oxidation pathway into cyanobacteria to supplement additional electrons to stimulate bacterial growth. This strategy conferred contamination resistance and enabled the utilization of phosphite-rich wastewater. A series of chemicals including raspberry ketone, indigo and its derivatives were effectively synthesized via SCHB, and the synthesis efficiency was promoted by a factor of up to 305%. Furthermore, the scalability of SCHB was demonstrated at the 500-litre level with real wastewater, which synchronized chemical production with nutrient recovery. Life-cycle assessment and techno-economic analysis indicated notable environmental benefits and economic feasibility. This study potentially opens a viable approach for the sustainable biosynthesis of chemicals. Bio-photosynthesis has the potential to achieve sustainable chemical production, but technical challenges remain. This work proposes a solar–chemical hybrid-driven biosynthesis strategy to achieve efficient chemical production from wastewater and carbon dioxide.

Microbial cell factories offer a sustainable route to plant-derived natural products, but yield drift and strain degeneration persist. Growth-coupled biosynthesis can continuously enrich high producers, yet specific product-responsive biosensors remain scarce and their population-level effects are unclear. Here, we describe a rapid transcriptome-mining workflow that, as proof-of-concept, delivers yeast biosensors for glycyrrhetinic acid and medicarpin. By fine-tuning PDR5 promoter, we expand the dynamic range of the glycyrrhetinic acid sensor and wire it to an essential gene, establishing a growth-addiction circuit that increases titer by 46.8 % after subculture. Single-cell transcriptome reveals that the evolved strain population exhibits a completely different division of labor compared to the initial strain. Coupling does not eliminate phenotypic heterogeneity; instead, it amplifies a dedicated sub-population marked by discrete transcriptional signatures. Deletion of genes highly expressed in non-producing cells or enrichment of high-producing cell clusters can further boost population-level production. This study provides both a generalizable biosensor-discovery platform and single-cell-guided strategies for stabilizing and optimizing natural-product cell factories. Growth-coupled biosynthesis in microbes can stabilise production yields, yet their population-level effects are unclear. Here the authors use ScRNA-seq to reveal that an evolved glycyrrhetinic acid-producing growth-coupled yeast strain population achieves division of labor.

Sustainable materials are needed to address the serious economic and safety risks of microbial metal corrosion. Colonizing metal surfaces with biofilms of noncorrosive microbes was previously shown to reduce aerobic, abiotic corrosion. However, the ability of biofilms to thwart highly corrosive anaerobic microbes is untested. Here we report on a strain of Escherichia coli genetically modified for enhanced metal adherence and adaptively evolved to tolerate sulfide. The E. coli biofilms effectively inhibited all known major routes for anaerobic microbial iron corrosion, including proton and sulfide attack, as well as the highly aggressive corrosion of electroactive microbes that directly extract electrons from Fe0. The E. coli biofilms prevented corrosion much better than biofilms of other microorganisms previously reported to reduce aerobic, abiotic corrosion. The results highlight the possibility of tailoring biofilm properties to function as effective sustainable, self-healing coatings to safeguard critical metal infrastructure.

Prime editing has emerged as a precise and powerful genome editing tool, offering a favorable gene editing profile compared to other Cas9-based approaches. Here we report several nCas9-DNA polymerase fusion proteins and their engineered versions to create a simple and efficient two-component chimeric oligonucleotide-directed editing (CODE) system. CODE contains a derivative of Bst DNA polymerase engineered for increased thermostability and processivity as well as a chimeric pegRNA (cpegRNA) for programmable search and replace genome editing. Additionally, CODEMax(exo+) features a 5’ to 3’ exonuclease activity that promotes effective strand invasion and repair outcomes favoring the incorporation of the desired edit. We demonstrate that CODEs can perform small insertions, deletions, and substitutions with improved efficiency compared to PEMax at many loci in HEK293T cells with plasmid- and RNP-based delivery. We also show that CODEMax can successfully modify mouse and bovine embryos with up to 9.3% precise editing. Further optimization of CODEMax systems may enhance editing outcomes in embryos and other challenging contexts. Overall, CODEs complement existing prime editors to expand the toolbox for genome manipulations without double-stranded breaks. Gene editing technologies enable precise DNA modifications but remain limited by efficiency, precision of intended edits, and flexibility. Here, authors develop chimeric oligonucleotide-directed and Cas polymerase-based systems that enhance programmable gene correction across cells and embryos.

High-salinity conditions frequently impair the fermentation performance of Saccharomyces cerevisiae in industrial processes involving high-osmolarity substrates. Identifying genetic determinants that enhance salt tolerance is therefore essential for the development of robust yeast cell factories. In this study, a comparative transcriptomic analysis was performed to investigate the transcriptional responses of a salt-tolerant strain, E-158, and its parental strain, KF-7, under 1.25 M NaCl stress, with the aim of identifying potential targets for strain engineering. Comparative transcriptomic analysis revealed extensive transcriptional differences between E-158 and KF-7 under high-salt conditions, involving central carbon and nitrogen metabolism, peroxisome-associated oxidative stress responses, ion transport, cell wall-related processes, and sporulation-related pathways. Based on these profiles, two transcription factors (CUP9 and ZNF1) and three functional genes (DAL1, IDP2, and CTA1) were selected for functional validation. Overexpression or deletion of the transcription factors, as well as overexpression of the functional genes, was carried out in KF-7. Fermentation experiments under 1.25 M NaCl demonstrated that all engineered strains outperformed the parental strain. Among them, overexpression of CTA1 resulted in the greatest improvement, with glucose consumption and ethanol production increased by 35.04% and 45.66%, respectively, after 96 h of fermentation. This study demonstrates that comparative transcriptomics can serve as an effective strategy for identifying engineering targets associated with salt tolerance in S. cerevisiae. The evaluated genes provide potential targets for strain improvement and offer insights for the rational design of yeast cell factories suited for high-salinity biofuel and bioproduct fermentation processes.

The global rise of antimicrobial resistance (AMR) demands urgent attention. While genetic drivers are well studied, epigenetic mechanisms, particularly DNA methylation, are emerging as key contributors to bacterial adaptation under antibiotic pressure. This review examines the roles of N6-methyladenine (m6A), N4-methylcytosine (m4C), and 5-methylcytosine (m5C), each catalyzed by distinct DNA methyltransferases (MTases), in regulating resistance-related processes such as efflux pump expression, β-lactamase activity, and stress responses. Advances in long-read sequencing technologies, including SMRT and ONT, now enable single-base resolution detection of methylation and support strain-specific methylome mapping. These efforts reveal methylation patterns that are dynamic, strain-dependent, and environmentally responsive, complicating resistance profiling. Emerging applications for tackling methylation-linked AMR include methylation-aware diagnostics and CRISPR-based epigenetic editing. Tools like CRISPR-dCas9 fused to DNA methyltransferases enable targeted, reversible suppression of resistance genes regulated by methylation. Current findings position DNA methylation as both a regulator of AMR and a promising target for next-generation diagnostics and therapeutics. However, challenges remain, including the lack of validated biomarkers, inconsistent protocols, and difficulty interpreting mixed-species data. Integrating methylation profiles with transcriptomic and phenotypic data will be essential to fully understand and target resistance mechanisms.

Human virome research is gaining increasing attention as viruses are recognized as critical modulators of microbial communities and human health. Viral metagenomics, however, faces unique challenges, including the low abundance and diversity of viruses in biological samples, the absence of universal marker genes, and biases introduced by experimental protocols. While various virome protocols have been benchmarked using viral particles or nucleic acids from mock communities, these approaches often fail to capture the complexity and heterogeneity of natural viromes. In this study, we systematically evaluated modifications to key methodological steps in the metagenomic analysis of human fecal samples, including viral enrichment, nucleic acid extraction, genome amplification, and library preparation. Using gold-standard bioinformatic approaches on sequencing datasets generated after amplification, we assessed the impact of these modifications on relative viral taxonomic assignment, contig quality, richness, diversity, and inferred genome structure. Our findings reveal striking trade-offs between recovery of viral genomes and retention of non-viral sequences, demonstrating how methodological choices can shape the inferred virome composition. Based on these observations, we propose an optimized protocol that enhances viral genome recovery while reducing contamination from non-viral sequences. This refined workflow provides a more robust and reliable framework for gut virome studies, paving the way for a deeper exploration of the role of viruses in human health and microbial ecosystems.

From aircraft to neural networks, engineers are often inspired by biological systems; however, literature often conflates inspiration with scientific evidence. Here, I propose a transparent and consistent reporting framework for bio-inspired design that can accelerate technological progress and stimulate collaborative scientific pursuits. From aircraft to neural networks, engineers are often inspired by biological systems; however, literature often conflates inspiration with scientific evidence. Christina Harvey proposes a transparent and consistent reporting framework for bio-inspired design that can accelerate technological progress and stimulate collaborative scientific pursuits.

Triggering immune response through generation of signal molecules is a common immune strategy across all domains of life. In the bacterial type IV Thoeris antiphage system, a Toll/interleukin-1 receptor (TIR)-domain protein produces adenosine 5’-diphosphate-cyclo[N7:1”]-ribose (N7-cADPR) as the immune signal to activate a Caspase-like effector. Here, we identified an inhibitor of type IV Thoeris through a phage mating assay that allows a sensitive phage to acquire anti-defense genes from related resistant phages. The inhibitor (hereafter TadIV-1) functions as a sponge that sequesters the N7-cADPR signal to inhibit Caspase activation. Structural analyses of TadIV-1 indicate a distinctive signal binding mechanism, wherein the binding pocket comprises its N-terminal flexible loop. In addition, phages lacking TadIV-1 can escape type IV Thoeris sensing through mutation in the capsid vertex protein. Collectively, this work expands the phage anti-defense arsenal with a unique immune signal sequestration mechanism and provides insights into phage invasion recognition mechanism of type IV Thoeris. The bacterial type-IV Thoeris system produces, in response to phage infection, a signal molecule that triggers protein degradation and stops viral replication. Here, the authors identify a phage protein that sequesters the signal, thus blocking the antiviral response.