bims-livmat Biomed News
on Living materials
Issue of 2025–03–30
six papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien
  1. Anti-Cancer Strategies Using Anaerobic Spore-Forming Bacteria Clostridium: Advances and Synergistic Approaches.
  2. Extracellular Bacterial Production of DNA Hydrogels-Toward Engineered Living Materials.
  3. CRISPRi-assisted metabolic engineering of cyanobacteria for photosynthetic hyaluronic acid from CO2.
  4. Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.
  5. Multistep Metabolic Engineering of Escherichia coli for High-Level Ectoine Production.
  6. Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.
  1. Life (Basel). 2025 Mar 14. pii: 465. [Epub ahead of print]15(3):
    Anti-Cancer Strategies Using Anaerobic Spore-Forming Bacteria Clostridium: Advances and Synergistic Approaches.
    Saloni Singh, Geun-Hyung Kim, Kwang-Rim Baek, Seung-Oh Seo.
      Despite ongoing advancements, cancer remains a significant global health concern, with a persistent challenge in identifying a definitive cure. While various cancer therapies have been developed and approved, offering treatments for smaller neoplasms, their efficacy diminishes in solid tumors and hypoxic environments, particularly for chemotherapy and radiation therapy. A novel approach, Clostridium-based therapy, has emerged as a promising candidate for current solid tumor treatments due to its unique affinity for the hypoxic tumor microenvironment. This review examines the potential of Clostridium in cancer treatment, encompassing direct tumor lysis, immune modulation, and synergistic effects with existing cancer therapies. Advancements in synthetic biology have further enhanced its potential through genetic modifications, such as the removal of alpha toxin gene from Clostridium novyi-NT, the implementation of targeted approaches, and reduction in systemic toxicity. Although preclinical and clinical studies have demonstrated that Clostridium-based treatments combined with other therapies hold promise for complete cancer eradication, challenges persist. Through this review, we also propose that the integration of various methods and technologies together with Clostridium-based therapy may lead to the complete eradication of cancer in the future.
    Keywords:  Clostridium; bacterial-cancer therapy; cancer; hypoxia; synthetic biology
    DOI:  https://doi.org/10.3390/life15030465
  2. Small. 2025 Mar 27. e2502199
    Extracellular Bacterial Production of DNA Hydrogels-Toward Engineered Living Materials.
    Philipp Gaspers, Christoph Bickmann, Christina Wallner, Daniel Baron Diaz, Dirk Holtmann, Johannes Gescher, Kersten S Rabe, Christof M Niemeyer.
      Engineered Living Materials (ELMs) combine synthetic biology with artificial materials to create biohybrid living systems capable of replicating, self-repairing, and responding to external stimuli. Due to their self-optimization abilities, these systems hold great potential for biotechnological applications. This study is a first step toward ELMs based on DNA hydrogels, focusing on the production of biohybrid materials using the exoelectrogenic bacterium Shewanella oneidensis. To equip the bacterium with the functionality needed for building DNA hydrogels, inducible cell surface anchors are developed, which can bind exogenous polymerase via the SpyCatcher/SpyTag (SC/ST) technology. The process parameters for in situ production of DNA hydrogels are established, enabling the development of these materials in the context of living bacteria for the first time. Using an extracellular nuclease-deficient S. oneidensis strain, stable biohybrid biofilms are generated directly on the surface of bioelectrochemical systems, showing the current generation. Given the high programmability and functionalization potential of DNA hydrogels, it is believed that this study represents a significant step toward establishing dynamic biohybrid material systems that exhibit both conductivity and metabolic activity.
    Keywords:  BES; DNA materials; S. oneidensis; biofilms; engineered living materials
    DOI:  https://doi.org/10.1002/smll.202502199
  3. J Biol Eng. 2025 Mar 27. 19(1): 26
    CRISPRi-assisted metabolic engineering of cyanobacteria for photosynthetic hyaluronic acid from CO2.
    Jigyeong Son, Hyun Jeong Lee, Han Min Woo.
       BACKGROUND: Hyaluronic acid (HA) is widely used in pharmaceuticals, medicine, and cosmetics. Sustainable production has shifted to microbial fermentation using engineered GRAS strains. Diverse carbon sources and CO2 conversion via engineered microorganisms enhance HA production. Herein we applied advances in CRISPR technologies and tools to optimize metabolic pathway by redirecting carbon portioning in cyanobacterium Synechoccous elongatus PCC 7942, demonstrating enhanced HA production.
    RESULTS: S. elongatus PCC 7942 lacking hyaluronan synthase (HAS) required pathway engineering for HA production. By expressing heterologous Class I HAS, a modular gene expression system was employed, incorporating hasB and hasC for the HA-GlcA module and glmU, glmM, and glmS for the GlcNAc module. This approach resulted in construction of four engineered cyanobacterial strains. Optimizing metabolic pathway involving the HA-GlcA and GlcNAc modules led to SeHA220 (wild-type with HA-GlcA and GlcNAc modules) producing 2.4 ± 0.85 mg/L HA at 21 d, a 27.5-fold increase compared to the control. Targeting F6P and G6P metabolic nodes via CRISPR interference to repress zwf and pfk genes further improved production, with SeHA226 (SeHA220 with a gene repression module) achieving 5.0 ± 0.3 mg/L HA from CO2 at 15 d. Notably, SeHA226 produced photosynthetic HA with a molecular weight (Mw) of 4.2 MDa, comparable to native producers, emphasizing the importance of precursor balance and growth conditions.
    CONCLUSIONS: This study engineered cyanobacteria for efficient HA biosynthesis using modular gene expression and CRISPR-interference systems. Optimizing heterologous metabolic pathway was key to achieving high-molecular-weight photosynthetic HA production from CO2. The findings provide insights into tunable HA production, with future efforts aimed at scaling up photosynthetic HA production for larger-scale applications.
    Keywords:  CRISPR-dCas12a; Cyanobacteria; Hyaluronic acid; Synthetic biology
    DOI:  https://doi.org/10.1186/s13036-025-00494-z
  4. Hum Vaccin Immunother. 2025 Dec;21(1): 2469416
    Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.
    Chinmay T Jani, Aysswarya Manoharan, Peter J DeMaria, Marijo Bilusic.
      Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulate an immune response. These biological entities including bacterial, yeast-based and viral vectors, have unique properties that can be harnessed to target and destroy cancer cells while eliciting a robust immune response. Clinical trials of cancer vaccines are investigating standalone and combination treatment strategies in the prophylactic, adjuvant, and palliative settings. This review offers insights into the current oncologic vaccine landscape and potential future development.
    Keywords:  Cancer immunotherapy; antigen cascade; cancer vaccine; immuno-oncology; live vector; therapeutic cancer vaccine; therapeutic vaccine; vaccine
    DOI:  https://doi.org/10.1080/21645515.2025.2469416
  5. ACS Synth Biol. 2025 Mar 25.
    Multistep Metabolic Engineering of Escherichia coli for High-Level Ectoine Production.
    Zheng Lei, Jinyong Wu, Caiwen Lao, Jin Wang, Yanyi Xu, He Li, Lixia Yuan, Xiangsong Chen, Jianming Yao.
      Ectoine is an important natural macromolecule protector that helps extremophiles maintain cellular stability and function under high-salinity conditions. Recently, the development of microbial strains for high-level ectoine production has become an attractive research direction. In this study, we constructed an efficient plasmid-free ectoine-producing strain. We modified the 5'-untranslated region of the ectABC gene cluster from Halomonas elongate to fine-tune the expression of genes ectA, ectB, and ectC. Furthermore, we optimized the carbon flow across the MEP pathway, the TCA cycle, and the aspartic acid metabolic pathway. Subsequently, we blocked the production of byproducts from the aspartic acid metabolic pathway and dynamically regulated the TCA cycle to coordinate the balance between strain growth and production. The final strain was tested in a 5-L fermenter, which reached 118.5 g/L at 114 h of fermentation. The metabolic engineering strategies employed in this study can be used for the biosynthesis of other aspartate derivatives.
    Keywords:  5′-UTR; Escherichia coli; ectoine; fed-batch fermentation; genome editing; metabolic engineering
    DOI:  https://doi.org/10.1021/acssynbio.4c00876
  6. Expert Opin Biol Ther. 2025 Mar 28. 1-14
    Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.
    Samantha Flores-Treviño, Paola Bocanegra-Ibarias, Daniel Salas-Treviño, María Teresa Ramírez-Elizondo, Eduardo Pérez-Alba, Adrián Camacho-Ortiz.
       INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.
    AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.
    EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.
    Keywords:  Dysbiosis; fecal microbiota transplantation; live biotherapeutic products; synthetic bacterial consortium; vaginal microbiota transplantation
    DOI:  https://doi.org/10.1080/14712598.2025.2484303
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