{"title":"Probiotics: From natural to artificial.","authors":"Li-Hua Liu, Xianhong Zhang, Ying Huang, Rongrong Chen, Junyang Huang, Shuqi Wang, Wei Li, Ao Jiang","doi":"10.1016/j.biotechadv.2026.108916","DOIUrl":"10.1016/j.biotechadv.2026.108916","url":null,"abstract":"<p><p>Probiotics are live microorganisms that confer significant health benefits by maintaining gut homeostasis, regulating immune function, and producing beneficial metabolites including short-chain fatty acids (SCFAs), bioactive peptides, and extracellular polysaccharides (EPSs). Most naturally isolated probiotics are severely limited by poor functional specificity, insufficient stress tolerance, and suboptimal performance. Driven by advances in multi-omics, mutagenesis breeding, and synthetic biology, the field has shifted from conventional natural screening to rational design and construction of artificial probiotics. This review systematically summarizes core technologies for developing high-performance artificial probiotics, including artificial intelligence (AI), high-throughput screening (HTS), directed evolution, genetic engineering, as well as scarless gene editing and in situ engineering. Applications of artificial probiotics span gut-organ axis regulation, medicinal-edible homologous (MEH) fermentation, targeted disease treatment, drug delivery, and environmental bioremediation. We also discuss major challenges concerning biosafety assessment, regulatory policies, in vivo adaptability, and dosage regulation. Finally, we highlight future directions toward personalized probiotics, aiming to provide a theoretical roadmap for research, clinical translation, and industrial application of next-generation artificial probiotics.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"108916"},"PeriodicalIF":12.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baojun Sun, Xiufeng Li, Di Cong, Shuang Li, Kequan Ning, Wei Xiang, Guoli Gong
{"title":"Recombinant human serum albumin-A paradigm shift: From laboratory development to industrial-scale production, and clinical translation.","authors":"Baojun Sun, Xiufeng Li, Di Cong, Shuang Li, Kequan Ning, Wei Xiang, Guoli Gong","doi":"10.1016/j.biotechadv.2026.108914","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2026.108914","url":null,"abstract":"<p><p>The transition from plasma-derived to recombinant human serum albumin (rHSA) represents a pivotal advancement in ensuring a safe and sustainable supply of this essential therapeutic protein. This review delineates the industrialization pathway of rHSA, highlighting yeast (Komagataella phaffii) and transgenic rice as the two dominant production platforms. Our analysis demonstrates that this paradigm arises not merely from considerations of yield, but from an optimal integration of scalability, cost-effectiveness, regulatory feasibility, and compatibility with next-generation purification strategies. Integrated multimodal purification technologies are critical for achieving the ultra-high purity required for high-dose therapeutic applications. We further synthesize clinical evidence confirming the biosimilarity and safety of rHSA produced from both platforms across key indications, thereby validating the entire technological pipeline from gene to final product. Looking ahead, we posit that the value of rHSA extends beyond substitution; its engineerability positions it as a versatile platform for innovative drug delivery and an essential animal-free component in advanced therapies. Realizing its full potential depends on overcoming the economic challenges of production scale-up, ensuring product consistency, and leveraging synthetic biology and intelligent manufacturing to pioneer a new generation of multifunctional biotherapeutics.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"108914"},"PeriodicalIF":12.5,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Lv, Bo Cai, Yong Xu, Yuandong Xu, He Liu, Jianchun Jiang, Kui Wang
{"title":"Progress and new approaches in the systematic integration of lignocellulose biorefinery technologies.","authors":"Yang Lv, Bo Cai, Yong Xu, Yuandong Xu, He Liu, Jianchun Jiang, Kui Wang","doi":"10.1016/j.biotechadv.2026.108913","DOIUrl":"10.1016/j.biotechadv.2026.108913","url":null,"abstract":"<p><p>Lignocellulose stands as the Earth's most abundant renewable organic carbon resource, representing a key pillar for achieving future carbon neutrality and advancing green biomanufacturing. While significant efforts have been devoted to developing various bioconversion strategies, including pretreatment and enzymatic hydrolysis techniques aimed at overcoming biomass degradation barriers, as well as fermentation and separation purification processes to achieve high-value components. The biorefining of lignocellulose is the coupling and integration of a series of technical units. The core challenge lies in the complex interplay between upstream and downstream units, which can exhibit both synergistic and inhibitory effects. This review provides a comprehensive overview of partial and whole-process integration strategies within lignocellulose biorefining. It further examines the key challenges and underlying mechanisms of unit integration, and focuses on exploring new strategies for deep integration based on novel pretreatment technologies. Finally, it is pointed out that achieving the uniform molecular weight of the lignocellulosic depolymerization products and the efficient utilization of all components will provide a new development path and broad prospects for the construction of the next-generation biorefinery platform.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"108913"},"PeriodicalIF":12.5,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-01-21DOI: 10.1016/j.biotechadv.2026.108809
Adam A. Aboalroub
{"title":"Advances in NMR Spectroscopy for biological systems: Principles, techniques, and their growing scope","authors":"Adam A. Aboalroub","doi":"10.1016/j.biotechadv.2026.108809","DOIUrl":"10.1016/j.biotechadv.2026.108809","url":null,"abstract":"<div><div>Nuclear Magnetic Resonance (NMR) spectroscopy is a crucial tool in structural biology, uniquely capable of revealing protein structure, dynamics, and interactions at atomic resolution in environments that closely resemble native conditions. The combination of key methodological breakthroughs—including strategic isotopic labeling, stronger magnetic fields, cryogenic probes, and advanced pulse sequences—has established NMR as the definitive method for gaining atomic-level insights into complex biomolecules, especially pathogenic proteins involved in disease. These advances enable various NMR techniques, from high-resolution solution and solid-state NMR (ssNMR) for insoluble assemblies to in-cell NMR. Beyond structural analysis, NMR provides robust quantitative performance, high reproducibility, and rich structural information, making it a valuable platform for biomolecular analysis and metabolomics. This review aims to provide a comprehensive overview of these critical roles, with a particular emphasis on the transformative influence of integrating Artificial Intelligence (AI) into NMR techniques to accelerate metabolomics-based biomarker discovery for various diseases and conditions.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108809"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-01-23DOI: 10.1016/j.biotechadv.2026.108810
Shu-Tong Wu , Xiao-Chuan Zheng , Chuan Chen , Zhong-Fang Sun , Kai-Kai Wu , De-Feng Xing , Shan-Shan Yang , Ai-Jie Wang , Nan-Qi Ren , Lei Zhao
{"title":"Biomanufacturing polyhydroxyalkanoates from CO2: A critical review of advances, challenges, and solutions for autotrophic and hybrid systems","authors":"Shu-Tong Wu , Xiao-Chuan Zheng , Chuan Chen , Zhong-Fang Sun , Kai-Kai Wu , De-Feng Xing , Shan-Shan Yang , Ai-Jie Wang , Nan-Qi Ren , Lei Zhao","doi":"10.1016/j.biotechadv.2026.108810","DOIUrl":"10.1016/j.biotechadv.2026.108810","url":null,"abstract":"<div><div>The bioconversion of carbon dioxide (CO<sub>2</sub>) into polyhydroxyalkanoates (PHAs) represents a transformative paradigm at the nexus of climate mitigation and sustainable manufacturing, offering a route to valorize a greenhouse gas (GHG) liability into high-value, biodegradable polymers. This critical review provides a systematic analysis of the technological landscape for CO<sub>2</sub>-to-PHA bioconversion, comparing the two dominant strategies: direct, single-organism autotrophic routes and modular, two-step hybrid systems that couple abiotic CO<sub>2</sub> reduction with microbial fermentation. While direct autotrophic processes offer conceptual simplicity, they exhibit a wide performance gap: photoautotrophs are typically constrained by low volumetric productivities (<10 mg L<sup>−1</sup> h<sup>−1</sup>) due to light limitation, whereas optimized chemoautotrophic systems (e.g., <em>Cupriavidus necator</em>) can achieve significantly higher rates of up to 1.55 g L<sup>−1</sup> h<sup>−1</sup>. In contrast, two-step hybrid systems show promise for modularity by decoupling CO<sub>2</sub> activation from biosynthesis. However, current integrated platforms generally demonstrate productivities in the milligram range (e.g., <25 mg L<sup>−1</sup> h<sup>−1</sup>). Critical bottlenecks, specifically inefficient gas-liquid mass transfer (low <em>k</em><sub>L</sub><em>a</em>), catalyst instability (<100 h lifetime), and the high energy penalty of downstream separation, persist across all platforms. Currently keeping production costs ($3–8/kg) well above the economic threshold. The path forward requires a strategic roadmap focused on three pillars: dynamic metabolic control via synthetic biology, process intensification using advanced reactor engineering, and holistic system integration. The successful convergence of these disciplines, supported by robust techno-economic frameworks and life-cycle assessments, is critical to transforming CO<sub>2</sub>-to-PHA bioconversion from a promising concept into a cornerstone technology for the circular bioeconomy.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108810"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-02-03DOI: 10.1016/j.biotechadv.2026.108814
Charandatta Muddana, Binbin Wang, Pei-Ti Sun, Yinjie J. Tang
{"title":"Comparative evaluation of large language models for biotechnology review writing","authors":"Charandatta Muddana, Binbin Wang, Pei-Ti Sun, Yinjie J. Tang","doi":"10.1016/j.biotechadv.2026.108814","DOIUrl":"10.1016/j.biotechadv.2026.108814","url":null,"abstract":"<div><div>Large language models (LLMs) are transforming how biotechnology review articles are conceived and written. This study evaluates LLMs in generating scientific review articles across three case studies with the focus on biomanufacturing and microbiology. Structured prompts were used across models under “Deep Research” modes, and both statistical and manual analysis (e.g., writing structure, citation metrics, critical depth, citation validity, and hallucination rate) were conducted. Results revealed that while LLMs can summarize large volumes of literature and generate structured outputs with coherent flow and illustrative tables, they fell short in critical analysis, quantitative reasoning, and citation reliability. “Pro” versions of LLMs produced more accurate and extensive citations than base versions, though issues of redundancy, bias toward specific Open Access publishers (e.g., MDPI, Frontiers), and occasional fabrication persisted. Among models, GPT-5 Pro was deeper in its analysis but had fewer citations. Gemini 2.5 Pro and the Perplexity Pro search engine retrieved broader literature with limited critique. Qwen 3 Max and DeepSeek R1 offered moderate balance, with the latter having higher hallucination rates in the application programming interface (API) version. Overall, “Pro” versions of LLMs generate decent summaries of reviewing topics but lack scholarly standards of novelty, rigor, and citation accuracy. Strategic integration and cross-validation of LLMs improve the quality of review papers. The findings underscore the need for new opinions, quantitative analysis or simulation, and interdisciplinary knowledge synthesis to publish valuable biotechnology reviews.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108814"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-01-31DOI: 10.1016/j.biotechadv.2026.108819
Qianmao Wen , Xinyu Li , Jiaxing Song , Junlin Xu , Yajie Meng , Leyi Wei , Zilong Zhang , Quan Zou , Feifei Cui
{"title":"Computational methods for signal peptide prediction: From statistical models to deep learning","authors":"Qianmao Wen , Xinyu Li , Jiaxing Song , Junlin Xu , Yajie Meng , Leyi Wei , Zilong Zhang , Quan Zou , Feifei Cui","doi":"10.1016/j.biotechadv.2026.108819","DOIUrl":"10.1016/j.biotechadv.2026.108819","url":null,"abstract":"<div><div>Signal peptides are short amino acid sequences located at the N-terminus of proteins. They guide newly synthesized proteins to their correct cellular destinations, playing a crucial role in protein localization and transport. Traditional experimental methods for identifying signal peptides are typically time-consuming, costly, and labor-intensive, driving rapid development of computational alternatives. Over the past two decades, researchers have proposed various computational approaches, with prediction accuracy continuously improving through evolution from early statistical and rule-based algorithms to deep learning. In this review, we systematically summarize these computational approaches, emphasizing methodological evolution and framework design. We compile representative computational methods, comparing their prediction outcomes and identifying existing limitations. Finally, we discuss current challenges and emerging opportunities, aiming to advance the development of computational frameworks characterized by unified evaluation, biologically grounded interpretation, and generative modeling.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108819"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-02-18DOI: 10.1016/j.biotechadv.2026.108846
Boting Li, Weifeng Liu
{"title":"Engineering microbial consortia for biosynthesis: Construction, regulation, and applications","authors":"Boting Li, Weifeng Liu","doi":"10.1016/j.biotechadv.2026.108846","DOIUrl":"10.1016/j.biotechadv.2026.108846","url":null,"abstract":"<div><div>Synthetic microbial consortia (SMCs) represent a paradigm shift from monocultures to multi-strain systems that leverage ecological interactions for enhanced environmental adaptation and bioproduction. This review systematically sorts out engineering strategies for constructing stable SMCs, focusing on three core principles regarding host selection based on obligate mutualism (e.g., auxotrophs), pathway modularization to resolve metabolic conflicts, and dynamic regulation using tools like quorum sensing and optogenetics. We demonstrate the efficacy of SMCs in diverse applications including high-value compound synthesis and lignocellulosic biomass conversion through consolidated bioprocessing and inhibitor mitigation. SMCs enabling advanced functions in engineered living materials, environmental remediation, and biomedical innovation via division of labor are also described. Despite such progress, challenges in scalability and real-time control of SMCs under industrial conditions remain. We conclude that SMCs serve to bridge evolutionary ecology and biotechnology, offering robust solutions for sustainable biomanufacturing and beyond.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108846"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-02-03DOI: 10.1016/j.biotechadv.2026.108833
Qian Liu , Qiu-Jun Liu , Shaohua Kang , Jiawei Li , Haotian Xia , Hao Qi
{"title":"From deep archival to real-time applications: Challenges and opportunities in DNA data storage","authors":"Qian Liu , Qiu-Jun Liu , Shaohua Kang , Jiawei Li , Haotian Xia , Hao Qi","doi":"10.1016/j.biotechadv.2026.108833","DOIUrl":"10.1016/j.biotechadv.2026.108833","url":null,"abstract":"<div><div>DNA has emerged as a highly promising next-generation data storage medium, offering unprecedented density, long-term durability, and low energy consumption compared to conventional storage technologies. Despite rapid advances, significant challenges remain across the entire spectrum of data storage scenarios—ranging from deep cold archival storage to hot, real-time data processing. For deep cold data, where data may not be accessed for decades, the primary requirements are extremely long-term preservation and maximized physical information density. Strategies such as silica encapsulation, porous photonic microspheres, and robust microbial chassis have demonstrated theoretical storage lifespans of centuries to millennia. In cold data scenarios, where files are accessed periodically, the ability to perform random access and repeated retrievals without data loss is critical. Advances in molecular indexing, microfluidic partitioning, and low-bias isothermal amplification offer promising solutions, while cellular systems provide a low-cost platform for repetitive readouts via high-fidelity replication. Warm and hot data storage presents the greatest technical barriers, including insufficient read/write throughput, high latency, and the lack of native support for dynamic data operations. Bridging this gap requires integration with automated, scalable molecular systems and further improvements in speed and reusability. Therefore, enabling the practical application of DNA storage across deep cold, cold, warm, and hot data scenarios will require sustained interdisciplinary efforts in molecular design, storage media engineering, and data retrieval strategies, along with system-level integration to meet the diverse demands of long-term durability, random access, and real-time responsiveness.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108833"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biotechnology advancesPub Date : 2026-05-01Epub Date: 2026-01-19DOI: 10.1016/j.biotechadv.2026.108806
Yi Shi , Lefei Wang , Yao Chen , Ling Jiang
{"title":"Recent advances in the covalent-bond-based peptide tagging systems and their applications","authors":"Yi Shi , Lefei Wang , Yao Chen , Ling Jiang","doi":"10.1016/j.biotechadv.2026.108806","DOIUrl":"10.1016/j.biotechadv.2026.108806","url":null,"abstract":"<div><div>Covalent bond–forming peptide tagging systems have emerged as powerful and versatile tools across a broad spectrum of biological and biotechnological applications. This review systematically summarizes the origins, molecular mechanisms of intramolecular covalent bond formation, major classes, and design strategies of peptide tagging systems. Based on their underlying chemistry, current systems are primarily categorized into isopeptide-bond-based and ester-bond-based platforms, both of which have demonstrated prominent utility in protein cyclization as well as <em>in vivo</em> and <em>in vitro</em> multi-enzyme assembly. Beyond these applications, isopeptide-bond-forming systems have been widely adopted as robust purification tags, whereas ester-bond-based systems offer unique opportunities for pH-responsive modulation of enzyme activity. Collectively, peptide tagging systems based on either isopeptide or ester bond formation represent an expanding and highly efficient toolkit for biotechnology. Continued advances in their design and application are expected to further broaden their functional scope and provide innovative solutions for future developments in protein engineering and related fields.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"88 ","pages":"Article 108806"},"PeriodicalIF":12.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}