Journal of Biological Engineering最新文献

{"title":"Are we there yet? The road to faster and more efficient CAR T cell manufacturing.","authors":"Leonor N Matos, Margarida S Costa, Margarida Serra, Marta H G Costa","doi":"10.1186/s13036-026-00666-5","DOIUrl":"10.1186/s13036-026-00666-5","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapies have achieved clinical success in autologous treatment of hematological malignancies. However, their broader application remains limited. Beyond the biological challenges associated with the immunosuppressive microenvironment of solid tumors and the graft-versus-host disease risks inherent to allogeneic settings, the widespread adoption of CAR T cells is hindered by the high costs, long and complex vein-to-vein timelines and variability in product quality. Rapid CAR T cell manufacturing has emerged as an alternative paradigm that prioritizes shortened production workflows and preservation of naïve and stem-like T cell phenotypes with superior in vivo expansion, persistence and anti-tumor efficacy. This review examines rapid CAR T cell manufacturing from a bioprocess engineering perspective, focusing on how critical process parameters can be explored to shape CAR T cell phenotype and function within shortened timelines. We highlight key technological enablers, including automation, microfluidic systems, process analytical technologies, artificial intelligence-driven bioprocess control, quality control methodologies as well as safety considerations unique to accelerated workflows. Emerging CAR T cell manufacturing models, such as point-of-care production and in vivo CAR T cells generation, are also discussed. These insights outline engineering strategies to enable faster, more consistent and clinically effective CAR T cells.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal deep learning for inflammatory bowel disease: a new frontier in cellular and molecular biomarker discovery to clinical translation.","authors":"Peihong Li, Siqing Guo, Yikun Zhang, Hongyi Hu, TingJun Cheng, Bo Xu, Kexin Zeng, Tianjiao Huang, Zhi Dong, BenHuo, Jiang Lin, Hongzhu Wen, Boyun Sun","doi":"10.1186/s13036-026-00637-w","DOIUrl":"10.1186/s13036-026-00637-w","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, relapsing condition with heterogeneous clinical phenotypes and variable therapeutic outcomes. Deep learning (DL), combined with high-throughput sequencing and multi-omics, has advanced precision management by enabling integration of genomic, transcriptomic, microbiome, metabolomic, imaging, and clinical data. DL applications include molecular biomarker discovery, automated endoscopic and histopathological image analysis, patient stratification, disease monitoring, and prediction of therapeutic response, such as anti-TNF-α efficacy. Convolutional neural networks (CNNs) demonstrate exceptional performance in image interpretation and automated scoring. Challenges for clinical translation include limited multi-center datasets, inconsistent annotations, low interpretability, and privacy concerns. Addressing these issues through interpretable, efficient, and privacy-preserving DL frameworks, along with temporally resolved cross-institutional datasets, will facilitate real-time monitoring and personalized care, reshaping IBD diagnosis, treatment, and long-term management.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"20 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-loaded hydrogels for bone regeneration: a cell-free therapeutic strategy.","authors":"Shengyu Jin, Shicheng Zhou","doi":"10.1186/s13036-026-00659-4","DOIUrl":"10.1186/s13036-026-00659-4","url":null,"abstract":"<p><p>Bone defects present significant challenges in clinical practice due to the limitations of traditional treatments. Compared to traditional cell therapies, exosome-based therapies have emerged as a promising alternative, offering a cell-free therapeutic strategy that harnesses the regenerative potential of stem cells. Exosome-based therapies are without the risks associated with live cell therapies, such as immune rejection and the complexities of large-scale cell culture systems. However, challenges such as stability and targeted delivery remain in the clinical translation of exosome therapies. To address these, recent advancements have focused on exosome-loaded hydrogels, which provide a controlled release system for exosomes, protecting them from degradation and ensuring sustained therapeutic effects at the bone defect site. These hydrogel systems offer an ideal environment for cell attachment, migration, and tissue formation, enhancing bone healing. This review explores exosomes in bone tissue engineering derived from mesenchymal stem cells (MSCs), adipose-derived stem cells (ADSCs), and other resources such as dental pulp stem cells (DPSCs), urine derived stem cells (USCs), and even skeletal stem cells (SSCs). Moreover, innovative strategies have been used to enhance the efficacy of exosome-based therapies, such as exosome mimetics‑loaded hydrogels as a scalable cell‑free strategy and “armored exosomes” as protective exosome formulations in functional hydrogels. There are challenges in clinical application, such as standardization of exosome production, long-term stability, immune response, and regulatory approval. Exosome-loaded hydrogels offer a scalable, effective, and safe alternative to traditional cell-based therapies in bone regeneration.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitin nanowhiskers/octacalcium phosphate synergistically reinforced chitosan hydrogel for enhanced bone regeneration.","authors":"Mingdong Yan, Yanjing Ou, Ruimin Liu, Changfu Xie, Jiang Chen","doi":"10.1186/s13036-026-00647-8","DOIUrl":"10.1186/s13036-026-00647-8","url":null,"abstract":"<p><p>The repair of jawbone defects faces critical challenges, such as the mechanical-bioactivity imbalance and limited bioactivity of traditional scaffold materials. This study proposes a “mechanical reinforcement–bio-mineralization” synergistic strategy to construct a chitin nanowhiskers (CHWs)/octacalcium phosphate (OCP) co-modified chitosan (CS) composite hydrogel (CS/CHWs-OCP) and systematically investigates its bone regeneration efficacy. Results demonstrate the successful fabrication of CS/CHWs-OCP hydrogels with gradient OCP loading (3%–12% wt). The hydrogels exhibit three-dimensional interconnected porous structures, favorable swelling properties, and effective protein loading/sustained-release capabilities. In vitro experiments reveal that CS/CHWs-OCPs significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenic differentiation of EA.hy926 cells, with the 12 wt% OCP group showing the highest alkaline phosphatase (ALP) activity. Micro-CT 3D reconstruction and histological analysis demonstrate that the 12 wt% OCP group exhibits optimal calvarial defect repair capacity, with its new bone volume fraction (BV/TV: 57.2 ± 10.2%) at 8 weeks being significantly superior to both the blank control and OCP-free hydrogel groups. In conclusion, the developed CS/CHWs-OCP hydrogel provides an effective solution for bone defect regeneration.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triphenylphosphine bromide enhances the effect of nano-micellar drug delivery system loaded with ROS inhibitor TEMPO on acute lung injury.","authors":"Jing Wang, Lisheng Xu, Wanrong Li, Fang Zhao, Yang Yang, Lingling Shan, Linyan Xin, Weiwei Wang","doi":"10.1186/s13036-026-00662-9","DOIUrl":"10.1186/s13036-026-00662-9","url":null,"abstract":"<p><p>BACKGROUND: Sepsis acute lung injury (ALI) is one of the common complications in sepsis. The molecular mechanism and treatment methods of acute lung injury in sepsis are unknown. AIM: The aim of this study was to prepare triphenylphosphine bromide (TPP)-polyethylene glycol-b-polycaprolactone (PEG-PCL) nano-micelles for the delivery of ROS inhibitor (TEMPO) [TEMPO@PP-PEG-PCL] in the treatment of acute lung injury (ALI). METHODS: TEMPO@TPP-PEG-PCL were prepared. The particle size, zeta potential and morphology of the TEMPO@TPP-PEG-PCL were determined. The stability, in vitro release, pharmacokinetics and critical micelle concentration of the TEMPO@TPP-PEG-PCL were determined. Lipopolysaccharide (LPS) was used to establish the models of ALI. in vivo and in vitro. Immunohistochemistry, western blot and immunofluorescence were used to evaluate the effects of TEMPO@TPP-PEG-PCL on mtDNA-cGAS-STING signal pathway in ALI. RESULTS: The particle size of TEMPO@TPP-PEG-PCL was (22.7 ± 0.3) nm and the zeta potential was (24.3 ± 0.4) mV. The transmission electron microscope showed that TEMPO@TPP-PEG-PCL were regular spheres. The results of fluorescence showed that TEMPO@TPP-PEG-PCL promoted the cellular uptake of drugs. Compared with TEMPO, TEMPO@TPP-PEG-PCL significantly decreased the level of intracellular ROS (P < 0.01) and mtDNA (P < 0.01) and the protein expressions of cGAS-STING-IRF3/NF-κB signal pathway(P < 0.01). CONCLUSIONS: Our results demonstrated that TEMPO@TPP-PEG-PCL were successfully prepared to deliver TEMPO for treatment of ALI. The mechanism was related to the regulation of cGAS-STING-IRF3/NF-κB signaling pathway. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modular biodevice assembly tool kit for combinatorial screening and benchmarking multiple cell surface display platforms in Escherichia coli.","authors":"Xiaoyue Xu, In-Geol Choi","doi":"10.1186/s13036-026-00660-x","DOIUrl":"10.1186/s13036-026-00660-x","url":null,"abstract":"<p><p>Bacterial cell surface display is a versatile platform technology for synthetic biology applications. A successful display platform often requires ad hoc testing of anchor scaffold types and orientations, as well as target protein types and orientations. To facilitate screening for the optimal display platform, this study designed and constructed a modular, combinatorial Escherichia coli surface display toolkit. The modular toolkit not only screens for the optimal combination of diverse anchor proteins to display various bioparts but also benchmarks the performance of multiple surface display platforms in E. coli simultaneously. The design of the modular toolkit was based on five representative types of anchor scaffolds encompassing autotransporters, outer membrane proteins, curli-associated proteins, and fimbriae-associated proteins. Both amino- and carboxy-terminal display was examined across 20 designs of full or truncated scaffolds, each combined with multiple signal peptides, promoters, and terminators. The combinatorial toolkit was validated and optimized using three display reporters with different sizes and features—sfGFP (fluorescence), agarase (enzymatic activity), and NanoLuc (luminescence). The optimal display combinations were primarily dependent on the orientation of anchor scaffolds, which varied with reporter properties. Strong promoters, such as T7, differentially affect surface display activity on substrate-dependent (agarase, NanoLuc) and substrate-independent (sfGFP) proteins, highlighting expression tuning as a critical parameter for surface display optimization. Using this modular kit, two previously uncharacterized anchor scaffolds (YdhQ and YcgV) were identified as functional for surface display. Finally, the applicability of the toolkit across multiple E. coli genetic backgrounds was confirmed, supporting its utility for diverse biotechnological applications.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147457589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing red blood cell compatibility: in vitro hemagglutination prevention using a trispecific triabody as a blocking fragment for blood group antigens.","authors":"Saleha Hafeez, Muhammad Asghar","doi":"10.1186/s13036-026-00661-w","DOIUrl":"10.1186/s13036-026-00661-w","url":null,"abstract":"<p><p>BACKGROUND: Access to safe and timely blood transfusion is a cornerstone of modern healthcare but depends on a stable supply of voluntary donations and rigorous hemovigilance systems. O-negative red blood cells are universally compatible and essential for emergency transfusions; however, their scarcity, particularly in low-resource regions, poses significant challenges. To address this challenge, a compact trispecific triabody was designed to block A, B, and Rh(D) antigens on RBCs. RESULTS: In this study, two triabody configurations differing in the placement of the anti-Rh(D) variable domain were generated, producing closed (C1) and open (O1) formats. The selected triabody-C1 was expressed in Escherichia coli BL21(DE3) and purified into two fractions, AE3-B1 and AE3-B2. Hemagglutination assays demonstrated that AE3-B2 did not induce hemagglutination, whereas AE3-B1 showed mixed-field hemagglutination under standard conditions and complete hemagglutination under potentiator-enhanced hemagglutination conditions. ELISA-based binding assays indicated that the triabody’s monomers functioned independently with free antigens, while RBC-bound antigen assays revealed altered binding behavior upon sequential antigen engagement. Blood incompatibility related hemagglutination assays using monoclonal antibodies and incompatible O-negative blood plasma demonstrated complete prevention of hemagglutination by AE3-B2 triabody-coated RBCs, confirming effective antigen blocking. CONCLUSIONS: The trispecific triabody efficiently prevents hemagglutination by blocking A, B, and Rh(D) antigens on RBCs, enabling them to exhibit enhanced compatibility and hemagglutinating patterns similar to O-negative cells. These findings provide a promising strategy to increase the pool of compatible blood for transfusion, particularly in emergency and resource-limited settings, while emphasizing that future in vivo investigations are needed to confirm efficacy and safety. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147457655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategic utilization of chicken bones immobilized by Aspergillus terreus for sustainable bioremediation of cobalt: statistical modeling, kinetics and thermodynamic studies.","authors":"Marwa Eltarahony, Eman H El-Gamal, Moustafa M Salama, Amany Ibrahim","doi":"10.1186/s13036-025-00599-5","DOIUrl":"10.1186/s13036-025-00599-5","url":null,"abstract":"<p><p>To address the environmental and health risks of cobalt, agricultural byproducts (peanut shells and luffa sponge), spent chicken bones, and sea sand were recruited as immobilization matrices for Aspergillus terreus. Their adsorptive performance toward cobalt (250 mg L−1 at pH 7 and 30 °C for 1 h) was evaluated. The fungi-immobilized chicken bones (At-I-CB) showcased superior adsorptive performance (45.42±0.66%) among other examined bio-carriers. To maximize biosorption efficacy, Box–Behnken design inferred that 8.7 g L−1 of At-I-CB could adsorb 103.04 mg L−1 of cobalt by 96.8% at pH 6.76 within 101.4 min. Characterization via EDX, FTIR and SEM confirmed the presence of signals and functional groups of the hybrid constituents with higher distribution of cobalt particles on the surface of fungal conidia/hyphae and hydroxyapatite, which implied the structural heterogeneity/porosity of bio-carrier. Such design furnished a potent stabilization and enhanced the adsorption performance. Meanwhile, kinetic analysis declared that cobalt biosorption onto At-I-CB followed chemisorption mechanisms via electrostatic interactions, ion exchange, and complexation. The most fitting model was Intra-Particle Diffusion (R2 = 0.99), followed by Fractional Power and Elovich (R2 = 0.96), reflecting multi-stage dynamics of adsorption including external surface interaction, internal pore diffusion, and boundary layer diffusion. Thermodynamic studies revealed maximum adsorption capacity (84.60%) at 75 °C, with positive ΔG° values unveiling a non-spontaneous process with favorability at higher temperatures. Further, enthalpy change (∆H°; 49.54 kJ/mol) emphasized the endothermic chemisorption. Remarkably, no study reported such a deeply detailed bio-adsorption capacity of novel At-I-CB. Finally, this study demonstrates the feasibility of biowastes recyclability and safe utilization as natural, sustainable and eco-benevolent fungal carriers for implementing sustainability goals and circular bioeconomy.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering NKG2D ligand affinity transforms EGFR-targeted NK cell engagers into high-potency effectors against pancreatic cancer.","authors":"Seul-Gi Lee, Myungjee Lee, Hye-Min Lee, Ga-Hyun Son, Sang-Rok Yoon, Byeong-Ho Chae, Dae-Seong Kim, Kyung-Mi Lee, Yong-Sung Kim","doi":"10.1186/s13036-026-00651-y","DOIUrl":"10.1186/s13036-026-00651-y","url":null,"abstract":"<p><p>BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) often escapes T cell–mediated immunity through impaired major histocompatibility complex class I (MHC-I) antigen presentation, contributing to its limited responsiveness to T cell–based immunotherapies. Because natural killer (NK) cells are capable of eliminating MHC-I–low tumor cells, redirecting NK cytotoxicity represents a promising strategy for these immune-cold tumors such as PDAC. Among activating NK receptors, NKG2D has been widely exploited in NK cell–engaging platforms through the incorporation of NKG2D ligands (MICA/B and ULBP family members). However, the impact of NKG2D ligand (NKG2DL) identity and binding affinity on NK cell engager potency has not been quantitatively defined. RESULTS: We engineered a panel of epidermal growth factor receptor (EGFR)–targeted, heterodimeric IgG1 Fc-based αEGFR×NKG2DL immune cell engagers (ICEs), each pairing a panitumumab-derived EGFR arm with one of six human NKG2DL extracellular domains (MICA, MICB, ULBP1, ULBP2, and the ULBP6 allelic variants ULBP0601 and ULBP0602). All ICEs bound specifically to EGFR and NKG2D, and NKG2D binding affinity correlated directly with NK cell cytotoxic potency across PDAC cell lines expressing different EGFR densities. Among native ligands, ULBP0602 exhibited the strongest NKG2D binding and highest killing activity. Yeast display–based affinity improvement of ULBP0602 yielded the variant ULBP6#2, which showed approximately a 13-fold improvement in affinity due primarily to slower dissociation kinetics. The affinity-improved αEGFR×ULBP6#2 induced up to an 11-fold reduction in EC₅₀ and greater maximal lysis than the parental construct, along with enhanced IFN-γ and TNF-α secretion by NK cells. In NK-humanized NSG mice bearing PDAC xenografts, αEGFR×ULBP6#2 achieved markedly greater tumor growth inhibition compared with αEGFR×ULBP0602 in both PANC-1 (89% versus 57%) and BxPC-3 (60% versus 25%) models, without observable toxicity or weight loss. CONCLUSIONS: These results support an affinity–activity relationship for NKG2D-engaging ICEs within the EGFR-targeted, Fc-competent format evaluated here. Notably, improving ULBP6 affinity enhanced NK cell effector function and increased antitumor efficacy in NK-reconstituted PDAC models. Collectively, our findings provide a design framework for engineering high-potency, tumor-tethered NKG2D engagers for the immunotherapy of immune-cold tumors such as PDAC. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid metabolic engineering enables xylose-driven co-production of polyhydroxybutyrate and violacein in Escherichia coli.","authors":"Khoi Nhat Pham, Eun Yeol Lee","doi":"10.1186/s13036-026-00653-w","DOIUrl":"10.1186/s13036-026-00653-w","url":null,"abstract":"<p><p>BACKGROUND: Within lignocellulosic biomass, xylose is the second most abundant sugar after glucose. As a renewable and sustainable substrate, it is gaining attention as a feedstock for microbial bioprocesses. In this study, we demonstrated the co-production of polyhydroxybutyrate (PHB) and violacein from xylose. We initially confirmed the feasibility of co-production through genome-scale metabolic simulations, followed by optimization using a hybrid expression system that combines a conventional tac promoter and synthetic promoter-ribosome-binding site-terminator (semi-endo PRT) elements in dual plasmids. Additionally, we assessed the antimicrobial activity of violacein against type I methanotrophs. RESULTS: Recombinant Escherichia coli DH5α harboring a hybrid system produced 111.3 ± 19.7 and 0.88 ± 0.23 mg/L of PHB and violacein, respectively, in M9 using xylose as the sole carbon source, without tryptophan supplementation. Using the synthetic PRT system, 528.9 ± 104 mg/g dry cell weight (DCW) of PHB was obtained. Additionally, violacein inhibits the growth of Methylomicrobium alcaliphilum 20Z at 9 µg/mL in nitrate mineral salt medium containing methanol as the sole carbon source. CONCLUSIONS: The use of lignocellulose-derived sugars for co-production offers an environmentally sustainable bio-manufacturing approach that contributes to greenhouse gas mitigation and supports the transition toward a circular bioeconomy. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}