Trends in Biotechnology

Recombinant collagen in the era of cellular agriculture Collagen is a foundational protein in both native tissues and engineered biomaterials. As cellular agriculture redefines protein production, recombinant collagen (RCOL) is emerging as a viable alternative to animal-derived collagen. RCOL offers molecular control, species-independent scalability, and integration into engineered cell systems. In this context, RCOL supports a closed-loop system: it is both a product of and an enabler for cellular agriculture, powering applications from cultivated meat to regenerative medicine. However, its performance is constrained by post-translational modifications (PTMs), including hydroxylation, glycosylation, and crosslinking, which govern triple-helix stability, fibrillogenesis, and bioactivity. This review discusses emerging strategies (enzyme coexpression, cotranslational incorporation, genetic modification, genetic code expansion, and photo-crosslinking) to bridge the PTM gap and advance RCOL platforms for cellular agriculture.

Online now: Recombinant collagen in the era of cellular agriculture

Epicardial patches for myocardial repair: circumventing barriers to heal ischemic heart tissue Ischemic heart disease, which leads to the loss of functional myocardium, remains the leading cause of death in late adulthood. Epicardial patches have emerged as a promising adjunctive strategy for myocardial repair. However, owing to the thick epicardial barrier (epicardial adipose tissue), only a select few approaches have demonstrated reduced scarring and improved heart function in large animal models and early-stage human trials. In this opinion article, we examine the different mechanisms and approaches to overcome the epicardial barrier. We further discuss key design and material considerations to improve safety and efficacy in clinical applications. Finally, we provide a summary of current regulatory and clinical challenges, together with proposed future research directions and foci in the translation of epicardial patches.

Online now: Epicardial patches for myocardial repair: circumventing barriers to heal ischemic heart tissue

Quantum computing for biotechnological innovation: transformative potential in biomedicine and drug discovery Quantum computing has emerged as a potential catalyst for addressing computational bottlenecks that increasingly constrain biotechnologies, including drug discovery, structural biology, and precision medicine. As biological datasets grow in scale and complexity, classical high-performance computing struggles to efficiently model molecular interactions and high-dimensional biological systems. Recent advances in hybrid quantum–classical algorithms and quantum-enhanced machine learning have enabled early proof-of-concept applications on noisy intermediate-scale quantum (NISQ) devices, offering new strategies for molecular simulation, pattern recognition, and optimization. In this opinion article, we critically assess where quantum computing may deliver realistic near-term value for biomedicine, emphasize hybrid workflows as the most viable path forward, and outline how quantum technologies could complement, not replace, existing computational paradigms as the field progresses toward fault-tolerant systems.

Online now: Quantum computing for biotechnological innovation: transformative potential in biomedicine and drug discovery

Recruiting orthogonal biological systems for engineering microorganisms Microbial synthetic biology focuses on the application of rational engineering strategies to reprogram microbial cells, thereby providing them with novel functions to meet different requirements. However, this engineering process inherently disrupts natural metabolism, leading to increased complexity and unpredictability within the metabolic system. To address these challenges, a series of orthogonal strategies has been developed and implemented in the construction of orthogonal genetic systems, metabolic pathways, energy systems, and regulatory systems. This review summarizes recent advances and applications of orthogonal strategies in microbial synthetic biology. Finally, future research directions in orthogonal microbial synthetic biology are explored, aiming to provide new insights for future studies.

Online now: Recruiting orthogonal biological systems for engineering microorganisms

Codon-optimized base editors enable efficient base substitution in Atlantic salmon Base editing is understudied in non-model fish. We developed codon-optimized base editors in a commercially important fish species, the Atlantic salmon, which demonstrate high editing efficiency and low off-target activity. Our efficient system created three fish lines bearing single-base loss-of-function mutations that mimic natural variation, which could facilitate regulatory approval.

Online now: Codon-optimized base editors enable efficient base substitution in Atlantic salmon

Industrial perspective validation of a neutralizer-free l-lactic acid production process by engineered acid-tolerant yeast Pichia kudriavzevii l-Lactic acid (l-LA) is one of the most important three-carbon chemicals in the world. Its crucial role as the precursor of polylactic acid (PLA) (see Glossary) has led to a soaring demand for l-LA [1]. The global demand for l-LA is estimated to reach $2.67 billion by 2030, at a compound annual growth rate of 11.2% from 2024 to 2030 (https://www.qyresearch.com/industry-news/7036/l-lactic-acid). Microbial fermentation is an industrial production strategy for l-LA. Corbion, NatureWorks, and Henan Jindan Lactic Acid Technology Co.

Online now: Industrial perspective validation of a neutralizer-free l-lactic acid production process by engineered acid-tolerant yeast Pichia kudriavzevii

Establishment of a nonhomologous end joining-mediated genomic library in Fusarium fujikuroi for high-level production of gibberellic acid NHEJ-mediated genome-wide insertional mutagenesis enables rapid discovery of functional genetic targets and stable integration sites in Fusarium fujikuroi, providing a versatile platform for metabolic engineering and strain improvement.

Online now: Establishment of a nonhomologous end joining-mediated genomic library in Fusarium fujikuroi for high-level production of gibberellic acid

Dengue nanosensors: a roadmap for clinical viability Dengue nanosensors promise much but have failed in clinical application. This paradox stems from a focus on record sensitivity over real-world robustness. We propose a paradigm shift from materials discovery to product engineering, providing a translational roadmap to guide viable diagnostics from the lab bench to the patient.

Online now: Dengue nanosensors: a roadmap for clinical viability

Biosensor-guided indexing of genome evolution for boosting microbial chemical synthesis This study developed a biosensor-driven genome evolution (BRIDGE) workflow that enables marker-free engineering of microbial hosts. As an example, protocatechuic acid (PCA) overproduction in Pseudomonas putida was achieved by BRIDGE. Considering the great variety of available biosensors, BRIDGE may represent a generalizable framework for biosensor-driven evolution of microbial cell factories.

Online now: Biosensor-guided indexing of genome evolution for boosting microbial chemical synthesis

Thermotolerant yeasts and their biotechnological applications Most known yeasts are mesophilic organisms, with optimal growth at 28–30°C. However, a few species, notably Ogataea polymorpha and Kluyveromyces marxianus, can grow at temperatures around 50°C. Their thermotolerance is of both fundamental and applied interest, offering advantages for high-temperature bioprocesses. Notably, cultivation at elevated temperatures facilitates simultaneous saccharification and fermentation (SSF) of starchy and lignocellulosic substrates, reduces sterility requirements, lowers distillation costs, and enhances the rates of biochemical reactions. These features make thermotolerant yeasts attractive platforms for producing biofuels, proteins, and other valuable compounds. Despite their potential, the underlying mechanisms of thermotolerance in these species remain underexplored. Herein, we systematically review the molecular, cellular, and metabolic mechanisms underlying yeast thermotolerance and discuss their implications for high-temperature industrial biotechnology.

Online now: Thermotolerant yeasts and their biotechnological applications

Trehalose 6-phosphate as master switch for optimizing crop yield and resilience Crop breeding faces the challenge of balancing yield with resource efficiency and stress tolerance. The key regulatory metabolite trehalose 6-phosphate (T6P) integrates carbon status with growth and stress responses. Manipulating T6P levels through genetic modification or chemical intervention provides a powerful tool to tackle the growing challenges of crop production.

Online now: Trehalose 6-phosphate as master switch for optimizing crop yield and resilience

Legal consequences of breaching a European mandatory regulation on genome-edited crops Genome editing enables targeted mutations indistinguishable from those in conventional breeding. In December 2025, the EU adopted more permissive regulations for some genome-edited crops, in line with other jurisdictions. We discuss consequences and principles available to stakeholders to protect their commercial interests should member states fail to comply with such regulations.

Online now: Legal consequences of breaching a European mandatory regulation on genome-edited crops

Online now: CRISPR genome editing in plants without tissue culture

The cellular harvest: a symbiotic road map for food sovereignty The ‘predatory replacement’ model in agriculture is untenable. We propose a symbiotic framework valorizing farmer-supplied agricultural waste side-streams to fuel bioengineered plant callus for decentralized high-value metabolite biosynthesis. Anchored in open-source governance and codesign, this approach shifts from displacement to innovation, reintegrating farmers to enhance sovereignty and resilience.

Online now: The cellular harvest: a symbiotic road map for food sovereignty

Advancements and challenges in CAR-NK cell therapy for cancer treatment Chimeric antigen receptor natural killer (CAR-NK) cell therapy is an emerging cancer treatment offering advantages over CAR-T therapy, including reduced risks of cytokine release syndrome and graft-versus-host disease. This review highlights how genetic engineering enhances natural killer cells’ innate tumor-killing abilities through CAR expression. Preclinical and clinical studies show promising antitumor responses, yet challenges remain, such as ensuring in vivo persistence, overcoming the immunosuppressive tumor microenvironment, and addressing manufacturing hurdles. Strategies such as cytokine support, combination therapies, and novel CAR designs are explored to improve efficacy. Future directions include personalized approaches, novel antigen targets, and artificial intelligence integration. CAR-NK therapy holds strong potential as a safe, scalable, and effective modality in cancer immunotherapy.

Online now: Advancements and challenges in CAR-NK cell therapy for cancer treatment

Growth-coupled evolution accelerates efficient biosynthesis of natural products Microbial natural product biosynthesis often suffers from metabolic burden and genetic instability. Bushin et al. introduce a synthetic C1 feedback loop that couples xanthommatin production to cell survival, enabling adaptive laboratory evolution to achieve gram-scale production. This strategy offers a generalizable route to engineer cell factories for complex natural products.

Online now: Growth-coupled evolution accelerates efficient biosynthesis of natural products

Multifunctional biosensors redefining liquid biopsy: advancing simultaneous multianalyte detection Liquid biopsy has revolutionized noninvasive disease diagnosis and monitoring by detecting circulating biomarkers such as tumor-derived DNA, miRNAs, proteins, exosomes, and circulating tumor cells in body fluids. Conventional single-analyte approaches fail to capture disease complexity, limiting diagnostic accuracy. Multifunctional biosensors enable simultaneous detection of multiple biomarkers, representing a paradigm shift in liquid biopsy. This review highlights recent advances in diverse detection strategies, including optical, electrochemical, plasmonic, and clustered regularly interspaced short palindromic repeats–based assays, alongside innovations in hybrid platforms, smart surface engineering, and nanotechnology. We also discuss integration with microfluidics, artificial intelligence, and chemometric analysis to enhance sensitivity, reduce signal interference, and improve scalability. Finally, challenges in clinical translation and standardization are highlighted, underscoring the transformative potential of multifunctional biosensors in precision medicine and early disease detection.

Online now: Multifunctional biosensors redefining liquid biopsy: advancing simultaneous multianalyte detection

Decode and rewire: programming Komagataella phaffii for bioproduction with synthetic transcriptional tools The yeast Komagataella phaffii is a leading producer of secreted therapeutic and industrial proteins. Its excellent traits make it a primary host for the production of value-added carbon compounds, including native metabolites, heterologous biomolecules, and synthetic chemicals. Recent breakthrough discoveries in engineering synthetic promoters have set the stage for novel bioprocesses that utilize sustainable carbon sources through directed evolution methods, ushering in a new era in bioindustry. This review discusses how engineering-directed transcriptional machinery element (TME) interaction-driven methodologies can unlock latent potential to rewire expression for the directed evolution of metabolic functions. We highlight discoveries in the design of transcriptional switches and metabolic switches, the reverse-engineering TME interaction via synthetic transcription factors, forcing K. phaffii for directed evolution.

Online now: Decode and rewire: programming Komagataella phaffii for bioproduction with synthetic transcriptional tools

Engineering Halomonas for low-salt, open, and unsterile production of polyhydroxybutyrate Wild-type Halomonas bluephagenesis TD1.0 was engineered to generate an iterative SSM series highly adapted to low-salinity conditions. The multiple strategy approach included genetic engineering, adaptive evolution, production module, and process engineering. Together, these synergistic strategies enabled the construction of broadly salinity-adaptive Halomonas chassis suitable for low-salinity, open, and nonsterile biomanufacturing.

Online now: Engineering Halomonas for low-salt, open, and unsterile production of polyhydroxybutyrate

Cultivated ingredients: a strategic pivot for cultivated meat? Cultivated meat is a promising solution to global food security challenges, but cultivated ingredients offer an equally compelling and potentially more economically stable path forward. Components such as flavour enhancers, cultivated fat, and proteins present scalable opportunities for improving alternative proteins, highlighting the untapped potential of cultivated ingredient-focused strategies.

Online now: Cultivated ingredients: a strategic pivot for cultivated meat?

An immune-inspired intelligent aptasensor with broad detection capability As analytical tools that convert biometric events into measurable signals, biosensors (see Glossary) are valuable in fields such as food safety, disease diagnosis, and environmental monitoring [1–4]. These systems typically comprise biological recognition elements (e.g., antibodies and aptamers) coupled with signal transduction modules (e.g., electrochemical, optical, and fluorescent), enabling highly specific target detection. The monitoring of key food contaminants, such as antibiotics, toxins, and heavy metal ions, necessitates the growing reliance on biosensors in food safety [5–8].

Online now: An immune-inspired intelligent aptasensor with broad detection capability

Elucidation of odd-chain dicarboxylate metabolism in Acinetobacter baylyi and application to polyethylene upcycling An integrated approach combines chemical degradation and biological conversion of postconsumer polyethylene waste into a value-added bioproduct in the nonmodel bacterium Acinetobacter baylyi ADP1. This study provides the genetic basis for applying synthetic biology and systems biology to construct a versatile microbial chassis for bio-upcycling plastic waste, thereby contributing to sustainable biomanufacturing.

Online now: Elucidation of odd-chain dicarboxylate metabolism in Acinetobacter baylyi and application to polyethylene upcycling

Broadening art–science collaboration in biotechnology: integrating design This article extends recent conversations on art–science collaboration in biotechnology to include design and biodesign. We highlight the rise of biodesign, tinkering with design, and more-than-human approaches in fostering innovative, sustainable outcomes for contemporary biotechnology, illustrating these opportunities through case studies in transdisciplinary partnership.

Online now: Broadening art–science collaboration in biotechnology: integrating design

Metabolic and enzyme engineering for steroid hormone biosynthesis Steroid hormones are key signaling molecules regulating growth, metabolism, reproduction, and stress adaptation and are widely used as essential pharmaceuticals. Traditional production from sterol feedstocks through multistep chemical or microbial transformations is limited by inefficiency and scalability. Recent advances in synthetic biotechnology enable de novo biosynthesis of steroid hormones from simple carbon sources in yeasts and fungi. This review highlights metabolic rewiring to increase flux, cytochrome P450 enzyme engineering for side-chain cleavage, and hydroxylation to overcome rate-limiting bottlenecks of steroid hormone biosynthesis. We also discuss strategies to redesign steroid-transport pathways to alleviate intracellular accumulation and improve membrane export. Looking ahead, we envision integrating metabolic, enzyme, and transport engineering to build a scalable, data-driven ‘intelligent’ platform for sustainable steroid hormone biomanufacturing.

Online now: Metabolic and enzyme engineering for steroid hormone biosynthesis

Biotechnology-driven artificial diets for mass-rearing arthropod natural enemies Arthropod natural enemies are central to biological control programs, where they regulate pest populations while contributing to ecological stability and biodiversity conservation. Nonetheless, for many species, large-scale rearing of these arthropods is constrained by expensive, labor-intensive methods that still rely heavily on living hosts. Emerging biotechnological tools promise to transform rearing practices by supporting the design of accurate, affordable, and host-independent artificial diets for arthropod natural enemies. This review explores biotechnology-driven advances in nutrient profiling, low-cost production, and functional packaging and integrates them into a unified framework. Moreover, this review highlights how the integration of multidisciplinary approaches and biotechnological innovations can address critical challenges in artificial diet development to enable sustainable biocontrol pest management at practical scales.

Online now: Biotechnology-driven artificial diets for mass-rearing arthropod natural enemies

Next-generation biosynthesis of human milk oligosaccharides Industrial biosynthesis of next-generation human milk oligosaccharides (HMOs) is hindered by glycosyltransferase (GT) promiscuity, metabolic imbalance, and chassis safety. This forum highlights advances in GT engineering, dynamic metabolic reprogramming, and Generally Recognized As Safe (GRAS) chassis development, aiming to ensure safe, precise, and efficient production of complex and diverse HMOs.

Online now: Next-generation biosynthesis of human milk oligosaccharides

The FDA’s plan to phase out animal testing Replacing animal testing through ‘New Approach Methodologies’ holds promise for developing cheaper and safer drugs without animal suffering. However, such an approach should be implemented carefully, and it cannot be rushed. We discuss the FDA Modernization Act 2.0 and 3.0 and the FDA’s roadmap to phase out animal testing.

Online now: The FDA’s plan to phase out animal testing

Image-guided volumetric bioprinting Image-guided volumetric bioprinting allows for the adaptive fabrication of complex structures for tissue engineering. Seminal work by Florczak et al. introduces Generative, Adaptive, Context-Aware 3D Printing, a workflow that uses computer vision to automatically generate functional, vascular-like networks that conform to living cells within hydrogels, improving their functionality.

Online now: Image-guided volumetric bioprinting

Systematic engineering of Micromonospora echinospora cell factory for gentamicin C1a overproduction Xu et al. establish an integrated strain–process engineering framework for efficient gentamicin C1a biomanufacturing. By combining genome-scale metabolic modeling, multi-gene regulatory optimization, metabolomics-guided flux analysis, and Bayesian-driven fed-batch control with in situ adsorption, the study reveals redox and energy metabolism as key constraints and enhances yield and productivity.

Online now: Systematic engineering of Micromonospora echinospora cell factory for gentamicin C1a overproduction

Precision insect control using programmable modular phage therapy platforms Spodoptera frugiperda (see Glossary), known as the fall armyworm (FAW), a highly polyphagous agricultural pest, is known to feed on over 350 plant species, including key economic crops such as maize, rice, soybean, and wheat [1]. According to the Food and Agriculture Organization (FAO), FAW inflicts direct economic losses exceeding $18 billion annually on maize crops in Africa, the Near East, and the Asia-Pacific region. The management of the FAW heavily relies on chemical insecticides such as chlorantraniliprole (CAP), leading to increasingly severe resistance issues [2,3].

Online now: Precision insect control using programmable modular phage therapy platforms