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Towards the application of nature's catalytic nanomachines: Cellulosomes in 2nd generation biofuel production
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-31 DOI: 10.1016/j.biotechadv.2025.108523
Maša Vodovnik , Nataša Lindič
Cellulosomes are highly efficient, complex multi-enzyme assemblies, predominantly found in anaerobic bacteria, which offer substantial potential for second-generation biofuel production through efficient lignocellulosic biomass degradation, thus reducing the need for costly pretreatments. Recent advances in cellulosome research have significantly contributed to developing more efficient consolidated bioprocessing (CBP) platforms for biofuel production. This review highlights the latest progress in designing cellulosomes for optimized enzyme synergy and substrate specificity, as well as advances in engineering cellulosome-producing whole-cell biocatalysts tailored for biofuel applications. Apart from recombinant approaches to the development of CBP platforms, metabolic engineering of cellulosome-producing strains (CPS) and co-culture systems that combine CPS with solvent-producing microbes are also discussed. Current challenges and future directions are outlined that emphasize the role of cellulosomes as powerful tools in advancing the efficiency of lignocellulosic biorefineries.
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引用次数: 0
Elucidation and biosynthesis of tetrahydroisoquinoline alkaloids: Recent advances and prospects
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-28 DOI: 10.1016/j.biotechadv.2025.108524
Yue Gao , Fei Li , Zhenbo Yuan , Zhengshan Luo , Yijian Rao
Tetrahydroisoquinoline alkaloids (THIAs) are a prominent class of plant-derived compounds with various important pharmaceutical applications. Considerable progress has been made in the biosynthesis of THIAs in microorganisms due to the elucidation of their natural biosynthetic pathways and the discovery of key enzymes. In this review, we systematically summarize recent progress in elucidating the natural biosynthetic pathways of THIAs and their biosynthesis in industrial microorganisms. In addition, recent advancements in the synthesis of THIAs through the construction of artificial multi-enzyme cascades and chemoenzymatic cascades are highlighted. Finally, the current challenges in developing efficient cell factories for producing THIAs are discussed, along with proposed strategies aimed at providing insights into the industrial production of THIAs.
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引用次数: 0
Cell-free systems: A synthetic biology tool for rapid prototyping in metabolic engineering
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-23 DOI: 10.1016/j.biotechadv.2025.108522
Kumyoung Jeung , Minsun Kim , Eunsoo Jang , Yang Jun Shon , Gyoo Yeol Jung
Microbial cell factories provide sustainable alternatives to petroleum-based chemical production using cost-effective substrates. A deep understanding of their metabolism is essential to harness their potential along with continuous efforts to improve productivity and yield. However, the construction and evaluation of numerous genetic variants are time-consuming and labor-intensive. Cell-free systems (CFSs) serve as powerful platforms for rapid prototyping of genetic circuits, metabolic pathways, and enzyme functionality. They offer numerous advantages, including minimizing unwanted metabolic interference, precise control of reaction conditions, reduced labor, and shorter Design-Build-Test-Learn cycles. Additionally, the introduction of in vitro compartmentalization strategies in CFSs enables ultra-high-throughput screening in physically separated spaces, which significantly enhances prototyping efficiency. This review highlights the latest examples of using CFS to overcome prototyping limitations in living cells with a focus on rapid prototyping, particularly regarding gene regulation, enzymes, and multienzymatic reactions in bacteria. Finally, this review evaluates CFSs as a versatile prototyping platform and discusses its future applications, emphasizing its potential for producing high-value chemicals through microbial biosynthesis.
{"title":"Cell-free systems: A synthetic biology tool for rapid prototyping in metabolic engineering","authors":"Kumyoung Jeung ,&nbsp;Minsun Kim ,&nbsp;Eunsoo Jang ,&nbsp;Yang Jun Shon ,&nbsp;Gyoo Yeol Jung","doi":"10.1016/j.biotechadv.2025.108522","DOIUrl":"10.1016/j.biotechadv.2025.108522","url":null,"abstract":"<div><div>Microbial cell factories provide sustainable alternatives to petroleum-based chemical production using cost-effective substrates. A deep understanding of their metabolism is essential to harness their potential along with continuous efforts to improve productivity and yield. However, the construction and evaluation of numerous genetic variants are time-consuming and labor-intensive. Cell-free systems (CFSs) serve as powerful platforms for rapid prototyping of genetic circuits, metabolic pathways, and enzyme functionality. They offer numerous advantages, including minimizing unwanted metabolic interference, precise control of reaction conditions, reduced labor, and shorter Design-Build-Test-Learn cycles. Additionally, the introduction of <em>in vitro</em> compartmentalization strategies in CFSs enables ultra-high-throughput screening in physically separated spaces, which significantly enhances prototyping efficiency. This review highlights the latest examples of using CFS to overcome prototyping limitations in living cells with a focus on rapid prototyping, particularly regarding gene regulation, enzymes, and multienzymatic reactions in bacteria. Finally, this review evaluates CFSs as a versatile prototyping platform and discusses its future applications, emphasizing its potential for producing high-value chemicals through microbial biosynthesis.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"79 ","pages":"Article 108522"},"PeriodicalIF":12.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036647","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}
引用次数: 0
Plant secondary metabolites against biotic stresses for sustainable crop protection
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-22 DOI: 10.1016/j.biotechadv.2025.108520
Tanzim Jahan , Md. Nurul Huda , Kaixuan Zhang , Yuqi He , Dili Lai , Namraj Dhami , Muriel Quinet , Md. Arfan Ali , Ivan Kreft , Sun-Hee Woo , Milen I. Georgiev , Alisdair R. Fernie , Meiliang Zhou
Sustainable agriculture practices are indispensable for achieving a hunger-free world, especially as the global population continues to expand. Biotic stresses, such as pathogens, insects, and pests, severely threaten global food security and crop productivity. Traditional chemical pesticides, while effective, can lead to environmental degradation and increase pest resistance over time. Plant-derived natural products such as secondary metabolites like alkaloids, terpenoids, phenolics, and phytoalexins offer promising alternatives due to their ability to enhance plant immunity and inhibit pest activity. Recent advances in molecular biology and biotechnology have improved our understanding of how these natural compounds function at the cellular level, activating specific plant defense through complex biochemical pathways regulated by various transcription factors (TFs) such as MYB, WRKY, bHLH, bZIP, NAC, and AP2/ERF. Advancements in multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, have significantly improved the understanding of the regulatory networks that govern PSM synthesis. These integrative approaches have led to the discovery of novel insights into plant responses to biotic stresses, identifying key regulatory genes and pathways involved in plant defense. Advanced technologies like CRISPR/Cas9-mediated gene editing allow precise manipulation of PSM pathways, further enhancing plant resistance. Understanding the complex interaction between PSMs, TFs, and biotic stress responses not only advances our knowledge of plant biology but also provides feasible strategies for developing crops with improved resistance to pests and diseases, contributing to sustainable agriculture and food security. This review emphasizes the crucial role of PSMs, their biosynthetic pathways, the regulatory influence of TFs, and their potential applications in enhancing plant defense and sustainability. It also highlights the astounding potential of multi-omics approaches to discover gene functions and the metabolic engineering of genes associated with secondary metabolite biosynthesis. Taken together, this review provides new insights into research opportunities for enhancing biotic stress tolerance in crops through utilizing plant secondary metabolites.
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引用次数: 0
Electrode functional microorganisms in bioelectrochemical systems and its regulation: A review 生物电化学系统中电极功能微生物及其调控研究进展。
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-13 DOI: 10.1016/j.biotechadv.2025.108521
Juping You , Lei Ye , Shihan Zhang , Jingkai Zhao , Yan Zhao , Yaxue He , Jianmeng Chen , Christian Kennes , Dongzhi Chen
Bioelectrochemical systems (BES) as environmental remediation biotechnologies have boomed in the last two decades. Although BESs combined technologies with electro-chemistry, −biology, and -physics, microorganisms and biofilms remain at their core. In this review, various functional microorganisms in BESs for CO2 reduction, dehalogenation, nitrate, phosphate, and sulfate reduction, metal removal, and volatile organic compound oxidation are summarized and compared in detail. Moreover, interrelationship regulation approaches for functional microorganisms and methods for electroactive biofilm development, such as targeted electrode surface modification, chemical treatment, physical revealing, biological optimization, and genetic programming are pointed out. This review provides promising guidance and suggestions for the selection of microbial inoculants and provides an analysis of the role of individual microorganisms in mixed microbial communities and its metabolisms.
生物电化学系统(BES)作为一种环境修复生物技术在近二十年得到了蓬勃发展。虽然BESs结合了电化学、生物和物理技术,但微生物和生物膜仍然是其核心。本文对BESs在CO2还原、脱卤、硝酸盐、磷酸盐和硫酸盐还原、金属去除和挥发性有机化合物氧化等方面的各种功能微生物进行了综述和比较。此外,还指出了功能微生物的相互关系调控途径和电活性生物膜的开发方法,如电极表面修饰、化学处理、物理揭示、生物优化和遗传规划等。本文为微生物接种剂的选择提供了有希望的指导和建议,并对混合微生物群落中单个微生物的作用及其代谢进行了分析。
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引用次数: 0
Advancements of astaxanthin production in Haematococcus pluvialis: Update insight and way forward 雨红球菌虾青素生产研究进展:最新见解和未来发展方向。
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.biotechadv.2025.108519
Hongli Cui , Xiaoli Zhu , Xiao Yu , Siming Li , Kang Wang , Le Wei , Runzhi Li , Song Qin
The global market demand for natural astaxanthin (AXT) is growing rapidly owing to its potential human health benefits and diverse industry applications, driven by its safety, unique structure, and special function. Currently, the alga Haematococcus pluvialis (alternative name H. lacustris) has been considered as one of the best large-scale producers of natural AXT. However, the industry's further development faces two main challenges: the limited cultivation areas due to light-dependent AXT accumulation and the low AXT yield coupled with high production costs resulting from complex, time-consuming upstream biomass culture and downstream AXT extraction processes. Therefore, it is urgently to develop novel strategies to improve the AXT production in H. pluvialis to meet industrial demands, which makes its commercialization cost-effective. Although several strategies related to screening excellent target strains, optimizing culture condition for high biomass yield, elucidating the AXT biosynthetic pathway, and exploiting effective inducers for high AXT content have been applied to enhance the AXT production in H. pluvialis, there are still some unsolved and easily ignored perspectives. In this review, firstly, we summarize the structure and function of natural AXT focus on those from the algal H. pluvialis. Secondly, the latest findings regarding the AXT biosynthetic pathway including spatiotemporal specificity, transport, esterification, and storage are updated. Thirdly, we systematically assess enhancement strategies on AXT yield. Fourthly, the regulation mechanisms of AXT accumulation under various stresses are discussed. Finally, the integrated and systematic solutions for improving AXT production are proposed. This review not only fills the existing gap about the AXT accumulation, but also points the way forward for AXT production in H. pluvialis.
由于天然虾青素(AXT)的安全性、独特结构和特殊功能,其潜在的人体健康益处和多种行业应用,全球市场对其的需求正在迅速增长。目前,雨生红球藻(Haematococcus pluvialis,又名湖生红球藻H. lacustris)被认为是天然AXT的最佳大规模生产者之一。然而,该行业的进一步发展面临两个主要挑战:由于依赖光的AXT积累,种植面积有限,AXT产量低,加上复杂,耗时的上游生物质培养和下游AXT提取过程导致的高生产成本。因此,迫切需要制定新的策略来提高雨杉AXT的产量,以满足工业需求,使其商业化成本更高。虽然筛选优秀的目标菌株、优化培养条件以获得高生物量产量、阐明AXT的生物合成途径、开发高含量AXT的有效诱导剂等策略已被应用于提高雨竹AXT的产量,但仍有一些未解决和容易被忽视的问题。本文首先综述了天然AXT的结构和功能,重点介绍了雨水藻AXT的结构和功能。其次,对AXT生物合成途径的时空特异性、转运、酯化和储存等方面的最新研究进展进行了综述。第三,我们系统地评估了提高AXT产量的策略。第四,讨论了不同应激条件下AXT积累的调控机制。最后,提出了提高AXT产量的综合系统解决方案。这一综述不仅填补了关于雨杉AXT积累的空白,而且为雨杉AXT的产生指明了方向。
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引用次数: 0
Recent advances in synthetic biology toolkits and metabolic engineering of Ralstonia eutropha H16 for production of value-added chemicals 富营养化Ralstonia eutropha H16合成生物学试剂盒及代谢工程研究进展。
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-09 DOI: 10.1016/j.biotechadv.2025.108516
Ye Wang , Yao Tian , Dake Xu , Shaoan Cheng , Wen-Wei Li , Hao Song
Ralstonia eutropha H16, a facultative chemolithoautotrophic Gram-negative bacterium, demonstrates remarkable metabolic flexibility by utilizing either diverse organic substrates or CO2 as the sole carbon source, with H2 serving as the electron donor under aerobic conditions. The capacity of carbon and energy metabolism of R. eutropha H16 enabled development of synthetic biology technologies and strategies to engineer its metabolism for biosynthesis of value-added chemicals. This review firstly outlines the development of synthetic biology tools tailored for R. eutropha H16, including construction of expression vectors, regulatory elements, and transformation techniques. The availability of comprehensive omics data (i.e., transcriptomic, proteomic, and metabolomic) combined with the fully annotated genome sequence provides a robust genetic framework for advanced metabolic engineering. These advancements facilitate efficient reprogramming metabolic network of R. eutropha. The potential of R. eutropha as a versatile microbial platform for industrial biotechnology is further underscored by its ability to utilize a wide range of carbon sources for the production of value-added chemicals through both autotrophic and heterotrophic pathways. The integration of state-of-the-art genetic and genomic engineering tools and strategies with high cell-density fermentation processes enables engineered R. eutropha as promising microbial cell factories for optimizing carbon fluxes and expanding the portfolio of bio-based products.
Ralstonia eutropha H16是一种兼性化能自养革兰氏阴性菌,它可以利用多种有机底物或CO2作为唯一的碳源,在有氧条件下H2作为电子供体,表现出显著的代谢灵活性。富营养菌H16的碳和能量代谢能力使合成生物学技术和策略得以发展,以设计其代谢,用于生物合成增值化学品。本文首先综述了真菌菌H16合成生物学工具的研究进展,包括表达载体的构建、调控元件的构建和转化技术。综合组学数据(即转录组学、蛋白质组学和代谢组学)的可用性与完全注释的基因组序列相结合,为高级代谢工程提供了强大的遗传框架。这些进展有助于对真菌素代谢网络进行有效的重编程。真核霉作为工业生物技术的多功能微生物平台的潜力进一步强调了它通过自养和异养途径利用广泛的碳源生产增值化学品的能力。将最先进的遗传和基因组工程工具和策略与高密度细胞发酵过程相结合,使工程化的真核生菌成为优化碳通量和扩大生物基产品组合的有前途的微生物细胞工厂。
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引用次数: 0
Advancement in synthetic gene circuits engineering: An alternative strategy for microRNA imaging and disease theranostics 合成基因电路工程的进展:microRNA成像和疾病治疗的替代策略。
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-09 DOI: 10.1016/j.biotechadv.2025.108518
Kulsoom , Wajahat Ali , Fu Wang
Gene circuits, which are genetically engineered systems designed to regulate gene expression, are emerging as powerful tools in disease theranostics, especially in mammalian cells. This review explores the latest advances in the design and application of gene circuits for detecting and treating various diseases. Synthetic gene circuits, inspired by electronic systems, offer precise control over therapeutic gene activity, allowing for real-time, user-defined responses to pathological signals. Notable applications include synZiFTRs for T-cell-based cancer therapies, immunomagnetic circuits for combating antibiotic-resistant infections like MRSA, and caffeine-induced circuits for managing type-2 diabetes. Additionally, advanced designs such as TetR-Elk1 circuits for reversing insulin resistance, RNAi circuits for targeting cancer cells, and synthetic circuits for managing metabolic conditions like urate homeostasis and diet-induced obesity are highlighted. These gene circuits, tailored for mammalian cells, showcase immense potential in gene- and cell-based therapies for complex metabolic and immune-related disorders, paving the way for precise, customizable treatments. The review focuses on the use of these circuits in mammalian systems and emphasizes their therapeutic implications, offering insights into future developments in disease treatment.
基因回路是一种旨在调节基因表达的基因工程系统,它正在成为疾病治疗的有力工具,尤其是在哺乳动物细胞中。本文综述了基因电路在检测和治疗各种疾病方面的设计和应用的最新进展。受电子系统启发的合成基因电路提供了对治疗性基因活动的精确控制,允许对病理信号进行实时的、用户自定义的反应。值得注意的应用包括用于t细胞癌症治疗的synZiFTRs,用于对抗耐抗生素感染(如MRSA)的免疫磁路,以及用于治疗2型糖尿病的咖啡因诱导电路。此外,先进的设计,如逆转胰岛素抵抗的ter - elk1电路,靶向癌细胞的RNAi电路,以及管理代谢条件的合成电路,如尿酸稳态和饮食诱导的肥胖。这些为哺乳动物细胞量身定制的基因回路,在复杂代谢和免疫相关疾病的基因和细胞治疗中显示出巨大的潜力,为精确、可定制的治疗铺平了道路。这篇综述的重点是这些电路在哺乳动物系统中的应用,并强调了它们的治疗意义,为疾病治疗的未来发展提供了见解。
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引用次数: 0
Corrigendum to “Recent advances in enzyme-enhanced immunosensors” [Biotechnology Advances 53 (2021) 107867]. “酶增强免疫传感器的最新进展”的勘误[生物技术进展53(2021)107867]。
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-08 DOI: 10.1016/j.biotechadv.2025.108515
Yanna Shao , Huan Zhou , Qingping Wu , Yonghua Xiong , Juan Wang , Yu Ding
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引用次数: 0
Mycelium-based composites: An updated comprehensive overview 菌丝体基复合材料:更新的综合概述
IF 12.1 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-06 DOI: 10.1016/j.biotechadv.2025.108517
Emma Camilleri , Sumesh Narayan , Divnesh Lingam , Renald Blundell
Mycelium-based composites hold significant potential as sustainable alternatives to traditional materials, offering innovative solutions to the escalating challenges of global warming and climate change. This review examines their production techniques, advantages, and limitations, emphasizing their role in addressing pressing environmental and economic concerns. Current applications span various industries, including manufacturing and biomedical fields, where mycelium-based composites demonstrate the capacity to mitigate environmental impact and enhance economic sustainability. Key findings highlight their environmental benefits, economic viability, and versatile applications, showcasing their potential to revolutionize multiple sectors. However, challenges such as consumer acceptance, intrinsic variability, and the need for standardized guidelines persist, underscoring the importance of further research and innovation. By optimizing material properties and refining production processes, mycelium-based composites could pave the way for widespread adoption as sustainable materials, contributing to a greener and more environmentally conscious future.
菌丝体基复合材料作为传统材料的可持续替代品具有巨大的潜力,为全球变暖和气候变化不断升级的挑战提供了创新的解决方案。本文审查了它们的生产技术、优点和局限性,强调它们在解决紧迫的环境和经济问题方面的作用。目前,菌丝体复合材料的应用跨越了各个行业,包括制造业和生物医学领域,在这些领域,菌丝体复合材料显示出减轻环境影响和提高经济可持续性的能力。主要研究结果强调了它们的环境效益、经济可行性和多用途应用,展示了它们在多个领域的革命性潜力。然而,诸如消费者接受度、内在可变性和对标准化指南的需求等挑战仍然存在,强调了进一步研究和创新的重要性。通过优化材料性能和改进生产工艺,菌丝体基复合材料可以为广泛采用可持续材料铺平道路,为更绿色、更环保的未来做出贡献。
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引用次数: 0
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Biotechnology advances
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