Deciphering and harnessing promoter-driven feedback controllers to mitigate metabolic burden in Corynebacterium glutamicum A genomically encoded GFP-based monitor enables real-time sensing of metabolic burden in C. glutamicum. Early burden-responsive promoters, including the conserved Pcg1940, are identified and coupled to feedback circuits that dynamically regulate gene expression, thereby improving cell growth, protein biosynthesis, and bioproduction in engineered cells.

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The genome editing revolution Table 1 of the published article contained an error attributing a milestone in DNA sequencing to Maxim instead of Gilbert. This error has been corrected. The authors regret the error.

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Recent advances in systems engineering approaches to integrated strain and bioprocess development Systems engineering has transformed chemical manufacturing, but bioprocessing has lagged in adopting comprehensive approaches. This review explores strategies that successfully engineer integrated upstream and downstream bioprocesses. Our analysis reveals a critical gap: bioprocess subsystems are typically optimized in isolation (‘subsystems optimization’), which limits the overall performance. We identify four key leverage points for systems engineering: engineering product accessibility to eliminate cell lysis, modifying strains to remove contaminants, adapting products for simplified purification, and enhancing strain tolerance for improved separation. While these integrative approaches substantially improve process consolidation, our findings show that there remains a significant misalignment between academic research and industrial needs (failing commercially relevant metrics). Embracing a holistic systems perspective is essential for future bioprocesses to have a transformative impact.

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Sulfur assimilation determines S-adenosyl-l-methionine flux for enhancing methylation efficiency in heterologous biosynthesis This study reveals that sulfur assimilation—specifically, the first reduction step of sulfate—has a determined impact on S-adenosyl-l-methionine flux compared with the C4 skeleton (activated form of l-homoserine). These findings offer a broadly applicable engineering strategy for the high-efficiency synthesis of diverse methyl-containing natural products with extensive practical applications.

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Selector adeno-associated viral vectors facilitate on-target precise genome editing and purge off-target chromosomal insertions This study establishes selector adeno-associated viral (AAV) vectors for the targeted and precise installation of chromosomal gene-sized edits. The incorporation of a marker-free co-selection system based on a cheap small molecule permits selector AAV vectors to, next to fostering targeted DNA editing, purge off-target chromosomal insertions, improving the quality of engineered cell products.

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Can nanozymes make the leap to the clinic? Advances, hurdles, and prospects Nanozymes (enzyme-like catalytic nanomaterials) represent a new generation of artificial enzymes designed to overcome key limitations of their natural counterparts, including high production costs, low stability, and challenging storage requirements. Their versatility spans biosensing, bioimaging, therapeutics, and environmental remediation, attracting widespread interest across disciplines. Recent advances have moved nanozymes beyond benchtop proof of concept, with multiple in vivo studies and early clinical investigations demonstrating their translational potential. However, progress toward the clinic remains constrained by limited mechanistic understanding under physiologically relevant conditions; concerns over safety, biodegradability, and long-term efficacy; and uncertainties in scalable manufacturing, market feasibility, and regulatory approval. This review highlights recent breakthroughs in biomedical nanozymes and identifies key knowledge gaps that must be addressed to accelerate successful clinical translation and commercialization.

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Reimagining aquatic toxicity testing through bioprinting Environmental toxicology relies on aquatic organisms to assess chemical safety, but ethical concerns are growing. We explore how bioprinting could be applied to aquatic models—from Daphnia analogs and bioprinted fish chorions to teleost-on-chip systems—to reduce live animal use while preserving regulatory relevance, highlighting key challenges and future directions.

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Multigram-scale stereoselective synthesis of neurosteroid isomers by gut microbial isolates using plant biomass-derived medium This research establishes a sustainable microbial platform for neurosteroid production using gut bacteria and plant-based materials. Three gut microbes with distinct stereoselectivities produce high-purity neurosteroid isomers including isopregnanolone. Key proteins such as bacterial 5α-reductase were characterized. The inherent stereoselectivity of whole-cell biotransformations eliminates chiral chromatographic separation, enabling cost-effective, scalable neurosteroid manufacturing.

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Cofactor engineering powers next-generation biomanufacturing Cofactor engineering is revolutionizing green biomanufacturing by overcoming the fundamental bottleneck between the limited supply/regeneration of cellular energy cofactors [e.g., NAD(P)H, ATP] and the high demands of efficient bioproduction. This review highlights advanced strategies, such as orthogonal systems that separate product synthesis pathways from basal metabolism, external energy sources (e.g., light or electricity) for cofactor regeneration, and material-enabled immobilization for scalable processes. These approaches enable high-yield production of diverse compounds, from specialized optically pure pharmaceuticals to bulk chemicals, by addressing critical limitations in yield, purity, and industrial scalability beyond conventional fermentation. Finally, we discuss challenges in process stability and economic viability, underscoring cofactor engineering’s potential as a versatile strategy for sustainable, next-generation biomanufacturing.

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Shaping cell therapy manufacturing with metabolic understanding and control The clinical efficacy of cell therapy products is intrinsically related to their state of differentiation and maturity. However, current approaches to target cell phenotype and potency lack efficacy, scalability, and cost-effectiveness. Metabolism is a key driver of cell fate, a characteristic that can be explored to design bioprocesses yielding functional cell therapy products. Here, we review recent studies focused on exploring metabolic shifts to improve cell potency and discuss how these strategies can contribute to accelerating bioprocess development and benefit from their translation into scalable, tightly controlled, and affordable manufacturing workflows.

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The liquidity paradox of the 505(b)(2) drug development pathway Regulatory pathways strongly influence how drugs are developed, financed, and sold. This article compares the FDA’s 505(b)(1) and 505(b)(2) routes, showing how the latter reduces both the development risk and the probability of postapproval transactions, and identifies strategies that can restore attractive, risk-adjusted investment returns.

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Clinical-scale bioreactor production of hiPSC-derived extracellular vesicles modulates miRNA and protein cargo to enhance angiogenic function A perfusion-based stirred-tank bioreactor enables scalable production of human induced pluripotent stem cell–derived extracellular vesicles (EVs) enriched in proangiogenic cargo. This approach overcomes key limitations of conventional EV production, delivering high yields and consistent quality, and represents an important step toward standardized, clinically relevant EV manufacturing for cell-free regenerative therapies.

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Engineered phage-derived lysins effectively kill mycobacterial pathogens Treatment of mycobacterial infections is difficult due to poor penetration of antibiotics across the complex cell envelope. We engineered phage-inspired lytic proteins, mycolysins, that selectively breach this barrier and enable rapid bacterial clearance in pulmonary and wound infection models, highlighting a programmable biologic platform to enhance and shorten existing therapies.

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Synthetic M13 phage engagers expand CAR-T cell antigen recognition to overcome tumor heterogeneity This work reports a bacteriophage-based engager platform that simultaneously addresses antigen heterogeneity and functional exhaustion of chimeric antigen receptor T cells in solid tumors. It enables modular antigen redirection and eliminates immune suppression to improve antitumor responses.

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Harnessing fungal fermentation for waste-to-food conversion One-third of food produced globally is lost or wasted, resulting in significant greenhouse gas emissions and economic losses. New strategies are needed to minimize food and agricultural loss or waste (FALW) and mitigate these negative planetary impacts. Filamentous fungi—a diverse group of microorganisms including molds and mushrooms—offer a unique solution to the FALW problem. These organisms are nature’s recyclers, capable of breaking down complex organic biomass, including food matter. Additionally, many fungi are edible and have long been used in food fermentation, suggesting they could be used to convert waste into food. In this review, we discuss emerging strategies across genetics, bioprocessing, and gastronomy that enable the production of sustainable foods from readily available FALW.

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Biotech intellectual property ownership and commercialisation: navigating start-up interactions with the university Effective collaboration between biotech start-ups and universities is critical for translating academic discoveries. This article examines intellectual property ownership models, licencing strategies, and publication timing, offering practical, experience-derived guidance for founders and technology transfer offices to strengthen commercialisation outcomes.

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Harnessing TLS polymerases to direct nucleotide outcomes in base editing Base editors introduce defined DNA lesions rather than directly rewriting nucleotides, and these lesions must be processed by cellular DNA repair pathways. In glycosylase-mediated base editing, apurinic/apyrimidinic sites (AP sites) represent a critical decision point where the choice of repair pathway determines whether the outcome is a desired substitution or an unintended byproduct. Although product heterogeneity has long been considered an intrinsic limitation of base editing, recent mechanistic studies suggest competition among repair polymerases represents a major contributor. Evidence indicates translesion synthesis polymerases can serve as tunable resolvers by preferentially inserting specific nucleotides opposite AP sites. Engineering their recruitment and insertion preferences may shift base editing from a stochastic repair-dependent process toward a more predictable mode of nucleotide incorporation.

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Utilizing biomolecular condensates as electrochemical reactors Liquid–liquid phase separation and biomolecular condensates have received massive fundamental research interest in recent years. Yu et al. engineered self-assembling, genetically encoded biomaterials that function as electrochemical reactors. Their work demonstrates the great utility of these materials in nanoparticle synthesis, pollutant degradation, and inhibition of bacteria through artificial ferroptosis.

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Innovating biomanufacturing with coculture-based engineered living materials Coculture-based engineered living materials (CCB-ELMs) address the issue of poor stability in microbial coculture systems, which can be applied to biomanufacturing and CO2 conversion. This forum summarizes the latest research progress, core challenges, and future prospects of CCB-ELMs for sustainable biomanufacturing.

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Human brain organoids and stakeholders’ attitudes: evidence, gaps, and governance We review 13 empirical studies examining attitudes toward human brain organoid (HBO) research. Stakeholders tend to emphasize practical concerns—worries about commercialization, reproductive cloning, informed consent, and uncertainty about consequences—rather than issues related to consciousness. Based on these findings, we identify three priority areas for future ethical and policy discussions.

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In vitro platforms for reconstructing skin–microbiome interactions The growing recognition of the skin microbiome in regulating the host’s metabolic and immune functions has spurred the development of in vitro platforms designed to recapitulate their intricate interactions, aiding research into both skin–microbiome and microbe–microbe interactions within their distinct niches. Despite these efforts, challenges remain in dissecting skin–microbiome interactions, especially due to the absence of a standardized platform for the long-term coculture of bacterial and mammalian cells. In this review, we highlight the key components in modeling an in vitro skin ecosystem and discuss the therapeutic potential of skin commensals, including recent advances and applications for engineered live biotherapeutics targeting skin diseases, to underscore the translational value of in vitro skin–microbiome interaction studies.

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Genome-scale modeling for rational design of microbial cells and cocultures Microbial cell factories are powerful platforms for the sustainable production of chemicals, foods, medicines, and energy. Enhancing production efficiency requires a deep understanding of the underlying metabolic mechanisms. Over the past 3 decades, genome-scale models have enabled quantitative metabolic simulation and driven the development of algorithms for guiding rational metabolic engineering. In this review, we provide an overview of recent algorithms for microbial cell design and the most comprehensive evolutionary roadmap to date, emphasizing their development and implementation. We also summarize advances in modeling frameworks and algorithms for coculture design, compare algorithms for microbial cells and cocultures, and discuss emerging trends shaping future model and algorithm development.

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Companies: share cultivated meat breakthroughs publicly—here is how Cultivated meat could satisfy soaring global protein demand while dramatically reducing greenhouse gas emissions and the spread of zoonotic diseases such as avian flu. One challenge is that, instead of sharing relevant scientific discoveries, too many companies keep them under lock and key, which imperils the entire sector.

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Paenibacillus polymyxa cell factories for production of polymyxins Polymyxins synthesized by Paenibacillus polymyxa are critical for the treatment of multidrug-resistant infections, but production suffers from low yield and high cost. This forum article focuses on strategies for engineering P. polymyxa cell factories by optimizing genetic transformation systems, gene editing tools, and metabolic engineering strategies to enable sustainable polymyxin production.

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Virus-mediated genome editing in grasses Genetic transformation in monocots, especially grasses, remains challenging and limits genome-editing applications. Plant viral vectors offer a transformation- and tissue culture-free alternative. Representative systems, such as barley stripe mosaic virus and barley yellow striate mosaic virus, enable heritable editing in several grass species and show strong potential for development into advanced genome-editing platforms.

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Bioprospecting c-di-GMP-activated exopolysaccharides in bacteria: isolation of a novel atypical sphingan A cyclic diguanosine monophosphate-activated screening platform turns ordinary bacterial collections into treasure troves of novel exopolysaccharides, exemplified by a galacto-sphingan. This strategy reveals cryptic biomaterials poised for green applications in agrifood and medicine.

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Seamless vessel–microenvironment bioprinting reveals contact-dependent vascular communications Current bioprinting often creates artificial barriers that disrupt cell communication. Zhao et al. introduce a seamless, collagen-based platform that eliminates material interfaces. This continuous microenvironment enables the discovery of critical contact-dependent signaling mechanisms in vascular development and cancer progression, offering a versatile tool for dissecting complex tissue interactions.

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Breaking the immunosuppressive barrier: an armored CAR-M biotechnology with the original M1 phenotype dominance rescues antitumor immunity The immunosuppressive environment of solid tumors limits the efficacy of current chimeric antigen receptor macrophage (CAR-M) therapies. We report a novel armored CAR-M technology that can dominate the tumor microenvironment and revitalize antitumor immunity. This breakthrough opens up promising new avenues for cancer immunotherapy, particularly for the treatment of solid tumors.

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Biomimetic recombinant collagen with multicopy dual-targeted hemostatic motifs for enhanced hemostasis in surgical trauma A multicopy dual-targeted design strategy for recombinant collagen is presented. By integrating hemostatic motifs (GFPGER and GPP) in multiple copies within a single collagen chain, receptor binding is enhanced, leading to stronger platelet activation, fibrin formation, and improved in vivo hemostatic performance.

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Revolutionizing vision using corneal 3D printing Corneal diseases remain a leading cause of blindness, and corneal transplantation is the primary treatment for severe cases. However, the persistent shortage of donor corneas significantly limits this approach. Artificial corneas with engineered biomaterials designed to mimic the structure and function of native corneal tissue offer a promising alternative, and significant progress has been made, including FDA approval and clinical trials. Among emerging technologies, 3D printing enables personalized customization of implants tailored to patient needs, anatomy, and pathology. This method also enables precise control over the biomaterial composition and integration of living cells within the implant, enhancing post-transplantation regeneration. In this review, we examine the advancements in 3D-printed, proregenerative artificial corneas, focusing on innovative biofabrication and the challenges that remain in ensuring implant quality.

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