bims-livmat Biomed News
on Living materials
Issue of 2026–01–11
seven papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien
  1. Correction to "Engineered Lactiplantibacillus plantarum WCFS1 as a Biosensor Probe for Lung Cancer".
  2. [Engineered probiotic Escherichia coli Nissle 1917 for controlled delivery of lycopene].
  3. Engineered Lactobacillus expressing tumor-killing cytokines: a novel biotherapeutic.
  4. Engineered Lactococcus lactis expressing antimicrobial peptide HI: Enhanced survival and protection against ETEC in mice.
  5. CRISPR-Based Approaches to Engineer Nonmodel Bacteria for Bioproduction and Biotherapeutics.
  6. Stress-trained microalgae robots with probiotics backpack and intestinal brake for inflammatory bowel disease management.
  7. Edible mushrooms as emerging biofactories for natural therapeutics and oral biopharmaceutical delivery.
  1. ACS Synth Biol. 2026 Jan 07.
    Correction to "Engineered Lactiplantibacillus plantarum WCFS1 as a Biosensor Probe for Lung Cancer".
    Michael Brasino, Eli Wagnell, Elise C Manalo, Samuel Drennan, Jared M Fischer, Justin Merritt.
      
    DOI:  https://doi.org/10.1021/acssynbio.5c00915
  2. Zhongguo Zhong Yao Za Zhi. 2025 Oct;50(20): 5733-5741
    [Engineered probiotic Escherichia coli Nissle 1917 for controlled delivery of lycopene].
    Rui Li, Dong Wang, Xue-Li Zhang, Jian-Mei Luo, Zhu-Bo Dai.
      Escherichia coli Nissle 1917(EcN), a non-pathogenic probiotic strain isolated from the human gut, exhibits intrinsic intestinal colonization, tumor-targeting capability, and proven biosafety, which make it an ideal live delivery system. This study engineered EcN to achieve dual functionality in intestinal colonization and controlled release of active compounds. Starting with wild-type EcN, this study used lycopene biosynthesis as a proof-of-concept. First, lycopene biosynthetic genes under arabinose-inducible promoters were integrated into the EcN genome via CRISPR/Cas9, which generated the base strain EcN-C1. Subsequent overexpression of rate-limiting genes in the endogenous methylerythritol phosphate(MEP) pathway: including isopentenyl diphosphate isomerase(idi), 1-deoxy-D-xylulose-5-phosphate synthase(dxs), and farnesyl diphosphate synthase(ispA): enhanced lycopene production by 4.28-fold. Further integration of a heterologous mevalonate(MVA) pathway augmented precursor supply, resulting in a further 2.58-fold increase in yield, elevating titer to(15.24±0.87)mg·L~(-1)(11.04-fold over initial strain). Dose-and time-dependent arabinose induction enabled precise control of lycopene release across engineered strains: EcN-C1 to EcN-C4 exhibited titers spanning 0.02-1.38, 0.22-2.81, 0.67-5.90, and 1.24-15.24 mg·L~(-1), respectively. This system achieved an 800-fold dynamic range(0.02-15.24 mg·L~(-1)), demonstrating fine-tuned control over compound delivery. This work lays an important foundation for the development of novel delivery systems based on probiotics for active compound release.
    Keywords:  Nissle 1917(EcN); live delivery system; lycopene; probiotics
    DOI:  https://doi.org/10.19540/j.cnki.cjcmm.20250611.101
  3. Ann Med Surg (Lond). 2026 Jan;88(1): 1040-1041
    Engineered Lactobacillus expressing tumor-killing cytokines: a novel biotherapeutic.
    Muhammad Shahid Mehmood, Maryam Abid, Fatima Hajj.
      Cancer accounts for over 10 million deaths annually, with solid tumors responsible for nearly 90% of cases worldwide. Systemic cytokine administration remains limited by severe toxicity, high-dose interleukin-2 (IL-2) therapy induces grade 3-4 adverse effects in >60% of patients, and treatment-related mortality is around 4%. In this context, engineered Lactobacillus strains designed to express tumor-killing cytokines such as IL-12, IL-15, and TRAIL represent a novel biotherapeutic strategy that combines microbial safety with precision immune activation. Experimental evidence shows that Lactobacillus plantarum secreting IL-12 reduces colorectal tumor volume by 65%, L. casei expressing TRAIL decreases pancreatic tumor mass by 40%, and L. reuteri producing IL-15 enhances CD8+ T-cell infiltration by 45% and improves survival by 30% in murine models. These data illustrate that cytokine-expressing probiotics can replicate the efficacy of systemic cytokine therapy while avoiding dose-limiting toxicity. Integrating synthetic biology tools such as inducible promoters and biosafety kill switches further refines control and containment, making this a viable candidate for translational development. The convergence of immunotherapy and microbiome engineering thus establishes engineered Lactobacillus as a novel, locally acting, and low-toxicity antitumor biotherapeutic with the potential to reshape next-generation cancer treatment.
    Keywords:  IL-12; IL-15; TRAIL; cancer immunotherapy; cytokine delivery; engineered Lactobacillus; probiotics; translational oncology
    DOI:  https://doi.org/10.1097/MS9.0000000000004400
  4. J Biotechnol. 2026 Jan 02. pii: S0168-1656(25)00314-1. [Epub ahead of print]410 331-340
    Engineered Lactococcus lactis expressing antimicrobial peptide HI: Enhanced survival and protection against ETEC in mice.
    Mingyang Hu, Chongpeng Bi, Yuwen Li, Yutong Xue, Sina Cha, Lu Zhao, Chenyu Xue, Na Dong.
      The rising prevalence of antibiotic resistance underscores the urgent need for alternative strategies to manage pathogenic bacteria. Engineered probiotics offer a promising platform for delivering antimicrobial peptides (AMPs); however, their practical application remains constrained by challenges related to maintaining viability and in vivo functionality. This study focused on two main aspects: (1) optimizing a freeze-drying strategy for Lactococcus lactis/pNZC-Usp45-H-6 ×His (L. L/HI), which expresses the AMP HI targeting Escherichia coli, and (2) evaluating its protective efficacy against enterotoxigenic Escherichia coli (ETEC) infection in a murine model. Sorbitol at a concentration of 6 % (w/v) was identified as the most effective cryoprotectant for preserving bacterial viability after freeze-drying. In the ETEC infection model, oral administration of L. L/HI significantly alleviated intestinal injury by reducing bacterial colonization and lipopolysaccharide levels, alleviating inflammation, and restoring the expression of tight junction genes. Moreover, L. L/HI downregulated the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulated the anti-inflammatory cytokine IL-10 in ileal tissues. These findings demonstrate that oral administration of L. L/HI reduced the bacterial burden in the ileum of ETEC-infected mice and indirectly alleviated inflammation and intestinal barrier damage caused by ETEC infection. This study provides a novel approach for the translational application of engineered probiotics.
    Keywords:  Antimicrobial peptide; Escherichia coli; Intestinal barrier integrity; Lactococcus lactis; Lyophilization
    DOI:  https://doi.org/10.1016/j.jbiotec.2025.12.019
  5. Biochemistry. 2026 Jan 05.
    CRISPR-Based Approaches to Engineer Nonmodel Bacteria for Bioproduction and Biotherapeutics.
    Kangsan Kim, Jiwon Lee, Namil Lee, Byung-Kwan Cho.
      Microbial diversity encompasses vast genetic and functional capacities, with immense potential for biotechnological applications. Yet, most biotechnological advances have been confined to a narrow set of model organisms, leaving the broader repertoire of nonmodel microbes largely untapped due to species-specific barriers that hinder genetic manipulation. Over the past decade, the advent of CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated protein) systems has transformed microbial engineering by enabling precise, programmable, and scalable control of genomes and gene expression. Importantly, the relative independence of many CRISPR effectors from host cofactors has facilitated their use in microbes previously challenging to engineer, thus expanding opportunities to exploit their unique metabolic and biosynthetic traits. In this review, we summarize the major CRISPR-Cas toolkits and highlight recent innovations, with particular emphasis on translational applications in nonmodel organisms such as C1-gas-fixing acetogens, antibiotic-producing Streptomyces, and gut commensal Bacteroides. We emphasize three areas of emerging impact: engineering microbial cell factories for sustainable biomanufacturing, accelerating natural product discovery, and development of next-generation live biotherapeutics. Finally, we discuss current limitations and future opportunities, underscoring how the integration of genome editing, synthetic biology, and systems-level approaches is reshaping the landscape of microbial biotechnology.
    Keywords:  Bacteroides; CRISPR (clustered regularly interspaced short palindromic repeats); Streptomyces; microbial diversity
    DOI:  https://doi.org/10.1021/acs.biochem.5c00613
  6. Nat Commun. 2026 Jan 06. 17(1): 173
    Stress-trained microalgae robots with probiotics backpack and intestinal brake for inflammatory bowel disease management.
    Ruifeng Luo, Jinwei Liu, Linxin Dai, Tianshun Duan, Qingwen Zhang, Cheng Gao, Ruibing Wang.
      Inflammatory bowel disease (IBD) involves elevated intestinal reactive oxygen species (ROS) and microbial imbalance. A key challenge is that current delivery systems cannot adequately protect active agents, such as antioxidants and probiotics, through the harsh gastric environment nor precisely deliver them to inflamed intestinal sites. Here, we present the EcN@PDA@HP biohybrid robot, composed of stress-trained microalgae, probiotics, and an intestinal braking system, enabling rapid gastric passage and precise retention in inflamed regions. Stress-trained Haematococcus pluvialis (HP) developed a thickened cell wall for gastric resilience, maintained flagella-driven motility, and enhanced astaxanthin (AST) production. Polydopamine (PDA)-coated Escherichia coli Nissle 1917 (EcN) anchors onto HP via host-guest interactions. In vivo, PDA preserves EcN activity and enables specific adhesion to inflamed sites. By combining antioxidizing AST and bacteriotherapy, EcN@PDA@HP effectively alleviates male murine IBD models via ROS scavenging and microbiota restoration, offering a promising strategy for diverse IBD conditions.
    DOI:  https://doi.org/10.1038/s41467-025-66692-x
  7. Front Fungal Biol. 2025 ;6 1742455
    Edible mushrooms as emerging biofactories for natural therapeutics and oral biopharmaceutical delivery.
    Kevin Wang, Annie Wang, Byron Meade.
      Mushrooms have long served as both food and medicine, providing polysaccharides, terpenoids, phenolics, and peptides with diverse health benefits. Extensive studies have begun to clarify the molecular mechanisms underlying these therapeutic effects, which include anti-aging, immunomodulatory, anticancer, and anti-inflammatory activities. Translational research is progressing from preclinical models to clinical trials, reinforcing the biomedical potential of mushroom-derived compounds. Advances in fungal genetic modification and gene editing have further positioned edible mushrooms as promising platforms for recombinant biopharmaceutical production. Their eukaryotic protein-processing capacity, natural bioencapsulation, and GRAS (Generally Recognized as Safe) status make them well-suited for sustainable and orally deliverable therapeutics. Engineered mushrooms show strong potential as platforms for oral vaccines and recombinant protein production, bridging traditional medicinal use with modern molecular farming.
    Keywords:  edible fungi; fungal biotechnology; mushroom molecular farming; oral biopharmaceutical delivery; recombinant protein expression
    DOI:  https://doi.org/10.3389/ffunb.2025.1742455
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