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Building a lignin biofoundry: a review 木质素生物铸造厂的研究进展
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-30 DOI: 10.1016/j.copbio.2025.103377
Catharine E Bosman , Luvuyo Tyhoda , Johann F Görgens , Kim M Trollope
Lignin, a complex biopolymer, holds significant promise for sustainable bioconversion into high-value products and chemicals; however, its recalcitrance, variable composition, and low degradation rates limit industrial application. Naturally sourced enzymes remain insufficient, and mature commercial solutions are scarce. Synthetic biology opens new avenues for lignin biotransformation, particularly through biofoundries that automate the ‘design-build-test-learn’ cycle. These platforms can integrate robotics, data-driven biology, and artificial intelligence to expedite ligninolytic enzyme development. By enabling high-throughput screening, directed evolution, and biosensor-guided selection, lignin-focused biofoundries present a transformative framework for overcoming current limitations. This review explores recent biotechnological advances and highlights the potential of biofoundries to unlock lignin’s untapped economic and environmental potential.
木质素是一种复杂的生物聚合物,在可持续生物转化为高价值产品和化学品方面具有重要的前景;然而,它的顽固性、可变成分和低降解率限制了工业应用。天然来源的酶仍然不足,成熟的商业解决方案也很少。合成生物学为木质素的生物转化开辟了新的途径,特别是通过自动化“设计-构建-测试-学习”周期的生物铸造厂。这些平台可以集成机器人技术、数据驱动生物学和人工智能,以加快木质素分解酶的开发。通过实现高通量筛选、定向进化和生物传感器引导选择,以木质素为重点的生物foundry为克服当前的局限性提供了一个变革性的框架。这篇综述探讨了最近的生物技术进展,并强调了生物铸造厂解锁木质素未开发的经济和环境潜力的潜力。
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引用次数: 0
Advances in the microbial biosynthesis of therapeutic terpenoids 微生物合成治疗性萜类化合物的研究进展。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-28 DOI: 10.1016/j.copbio.2025.103374
Peter H Winegar , Maria CT Astolfi , Sara F Holm , Graham A Hudson , Jay D Keasling
Terpenoid natural products and their derivatives exhibit bioactivity that is utilized in FDA-approved drugs and candidates for future drugs; however, the widespread utilization of terpenoids has been limited by complex, low-yielding native biosyntheses and chemical syntheses. Microbial total/semi-biosynthesis of natural and new-to-nature terpenoids from sustainable feedstocks is scalable and can achieve economically viable cost targets. Herein, this review describes foundational advances in synthetic biology and metabolic engineering as exemplified by efforts to biosynthesize prominent terpenoids (i.e. artemisinin, taxol, vinblastine, QS-21, and cyclopamine) in engineered microorganisms (e.g. Escherichia coli and Saccharomyces cerevisiae). Emerging methods that accelerate microbial biosynthesis campaigns (i.e. automation, machine learning, artificial intelligence, and combinatorial screening) are then discussed.
萜类天然产物及其衍生物具有生物活性,可用于fda批准的药物和未来药物的候选药物;然而,萜类化合物的广泛利用受到复杂、低产量的天然生物合成和化学合成的限制。微生物从可持续原料中合成天然和新天然萜类化合物的总/半生物合成具有可扩展性,并且可以实现经济上可行的成本目标。在此,本文综述了合成生物学和代谢工程方面的基础进展,例如在工程微生物(如大肠杆菌和酿酒酵母)中生物合成重要萜类化合物(如青蒿素、紫杉醇、长春花碱、QS-21和环巴胺)的努力。然后讨论了加速微生物生物合成活动的新兴方法(即自动化,机器学习,人工智能和组合筛选)。
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引用次数: 0
Aromatic compound production by Corynebacterium glutamicum: unified strategies at the core and diversity by extension 谷氨酸棒状杆菌生产芳香族化合物:核心为统一策略,外延为多样性
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-24 DOI: 10.1016/j.copbio.2025.103372
Nora Junker , Sara-Sophie Poethe , Volker F. Wendisch
Aromatic compounds are an important class of natural substances with a wide range of physiological functions and, thus, applications in the food, feed, fine chemical, and plastics industries or as pharmaceuticals. As a prime player in industrial amino acid production, C. glutamicum is an ideal host to engineer the shikimate pathway for de novo biosynthesis of aromatic amino acids (AAAs) and derived arenes and heteroarenes. Recently, metabolic engineering strategies in this regard have converged, and potent AAA-producing strains have been developed. Three trends that will further expedite the field will be discussed: the use of alternative substrates, biofoundry approaches, and pathway extensions towards specialized metabolites with sought-after medical relevance.
芳香族化合物是一类重要的天然物质,具有广泛的生理功能,因此在食品、饲料、精细化工、塑料工业或药品中有着广泛的应用。作为工业氨基酸生产的主要参与者,谷氨酰胺是设计莽草酸途径的理想宿主,用于从头合成芳香氨基酸(AAAs)和衍生芳烃和杂芳烃。近年来,在这方面的代谢工程策略已经趋同,并开发了有效的生产aaa的菌株。将讨论将进一步加速该领域的三个趋势:替代底物的使用,生物铸造方法,以及向具有受欢迎的医学相关性的专门代谢物的途径扩展。
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引用次数: 0
Designed dietary fibers: engineering carbohydrate structure for precision modulation of the human gut microbiome 设计膳食纤维:工程碳水化合物结构,精确调节人类肠道微生物群
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-23 DOI: 10.1016/j.copbio.2025.103371
Marcelo Iñaki Guerrero Montalván , Mariana Guzmán Sánchez , Victoria Gutierrez , Yunus E Tunçil , Stephen R Lindemann
The human colonic microbiota exerts a profound influence on health, mediated by highly specific relationships among dietary fiber structures and microbial degraders. Systematic control of fiber structure offers opportunities to engineer microbiota-targeted interventions with increasing precision. Here, we examine the evolution of designed dietary fibers — biotechnologically produced oligosaccharides or polysaccharides synthesized de novo or naturally occurring polysaccharides intentionally modified post-extraction for their fine physical or chemical structures to influence gut microbiome. We propose a hierarchical framework to classify these fibers based on the degree of fine structure control, highlight current strategies for carbohydrate modification approaches, and discuss emerging directions for the field. Despite recent advances, much potential remains unrealized for the rational, reproducible design of microbiome-targeted fibers.
人类结肠微生物群通过膳食纤维结构和微生物降解物之间的高度特定关系对健康产生深远影响。纤维结构的系统控制提供了以越来越精确的方式设计针对微生物群的干预的机会。在这里,我们研究了设计膳食纤维的演变-生物技术生产的低聚糖或重新合成的多糖或天然存在的多糖有意修改提取后的精细物理或化学结构,以影响肠道微生物群。我们提出了一个基于精细结构控制程度的分层框架来对这些纤维进行分类,重点介绍了碳水化合物改性方法的当前策略,并讨论了该领域的新兴方向。尽管最近取得了一些进展,但合理的、可重复的微生物群靶向纤维设计仍有很大的潜力有待实现。
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引用次数: 0
Understanding methanol metabolism through systems biology: advances and future perspectives 通过系统生物学理解甲醇代谢:进展和未来展望。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-13 DOI: 10.1016/j.copbio.2025.103370
Haoyu Wang , Fan Bai , Hongzhong Lu , Yongjin J Zhou
Methanol represents a promising sustainable one-carbon (C1) feedstock for biomanufacturing. However, limitations arising from cytotoxicity and incomplete metabolic understanding have resulted in low production efficiencies and constraining industrial applications. Recent systems biology approaches, including multi-omics and computational modeling, have significantly advanced our knowledge of microbial methanol metabolism. Here, we first summarize recent methodological progress in systems biology applied to methanol metabolism studies. Secondly, we highlight novel insights into understanding methanol metabolism by applying systems biology approaches in natural and synthetic methylotrophic microorganisms. Finally, we discuss the challenges and future perspectives for systems biology studies of methanol metabolism in yeast.
甲醇是一种有前途的可持续的生物制造单碳(C1)原料。然而,由于细胞毒性和对代谢的不完全了解,导致生产效率低,限制了工业应用。最近的系统生物学方法,包括多组学和计算建模,大大提高了我们对微生物甲醇代谢的认识。在这里,我们首先总结了系统生物学应用于甲醇代谢研究的最新方法进展。其次,我们强调通过应用系统生物学方法在天然和合成甲基营养微生物中理解甲醇代谢的新见解。最后,我们讨论了酵母甲醇代谢系统生物学研究的挑战和未来前景。
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引用次数: 0
Emerging strategies to enhance microbial natural product–based drug discovery 新兴战略加强微生物天然产物为基础的药物发现
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-10 DOI: 10.1016/j.copbio.2025.103369
Michael Madden , Conor Pulliam , Katherine Holandez-Lopez , Andrew Campbell , Jie Li
Natural products (NPs) have served as a major source of chemically novel, bioactive therapeutics for the treatment of various diseases. In recent years, NP discovery has benefited greatly from advancements in biotechnological fields. This review covers techniques and tools from 2022 to 2025 that have expanded NP discovery capabilities through gene-editing tools to activate silent biosynthetic genes, cell-free methods for NP production and diversification, as well as artificial intelligence and informatics tools for structure generation and correlational studies.
天然产物(NPs)已成为治疗各种疾病的新型化学生物活性疗法的主要来源。近年来,NP的发现得益于生物技术领域的进步。本文综述了从2022年到2025年的技术和工具,这些技术和工具通过基因编辑工具来激活沉默的生物合成基因,用于NP产生和多样化的无细胞方法,以及用于结构生成和相关研究的人工智能和信息学工具,扩大了NP发现能力。
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引用次数: 0
Production of chemicals by metabolically engineered Escherichia coli 通过代谢工程改造的大肠杆菌生产化学物质。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-06 DOI: 10.1016/j.copbio.2025.103367
Gyudong Jang , Min-Jung Kim , Sang Yup Lee
Escherichia coli is increasingly employed for chemical production, with its industrial competitiveness now depending on both the expansion of its molecular repertoire through first-in-class pathways and achieving best-in-class titer, rate, and yield (TRY). Recent milestones include the first demonstration of producing aromatic homopolyester and poly(ester amide)s from glucose using engineered E. coli. To optimally maximize TRY, systems metabolic engineering leverages diverse tools such as genome-scale CRISPRi/sRNA libraries, dynamic biosensors, and redox-balancing modules to optimally channel cellular resources toward product formation. In parallel, in silico tools support retrobiosynthetic pathway design, flux optimization, and enzyme engineering. By integrating first-in-class pathway construction with best-in-class TRY optimization, E. coli is poised to drive the next generation of sustainable, large-scale biomanufacturing. Overall, this review outlines representative achievements, strategic approaches, and emerging prospects, highlighting how recent advancements are positioning E. coli as a versatile and competitive chassis for sustainable production of value-added chemicals and materials.
大肠杆菌越来越多地用于化学生产,其工业竞争力现在取决于通过一流途径扩大其分子库,并达到一流的滴度、速率和产量(TRY)。最近的里程碑包括首次演示使用工程大肠杆菌从葡萄糖生产芳香均聚酯和聚(酯酰胺)s。为了优化TRY,系统代谢工程利用多种工具,如基因组级CRISPRi/sRNA文库、动态生物传感器和氧化还原平衡模块,以优化细胞资源流向产品形成。同时,硅工具支持逆转录生物合成途径设计、通量优化和酶工程。通过将一流的途径构建与一流的TRY优化相结合,大肠杆菌有望推动下一代可持续的大规模生物制造。总体而言,本综述概述了具有代表性的成就、战略方法和新兴前景,强调了最近的进展如何将大肠杆菌定位为可持续生产增值化学品和材料的通用和有竞争力的底盘。
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引用次数: 0
Strategies for engineering domesticated and undomesticated human microbes 驯化和未驯化人类微生物的工程策略。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-04 DOI: 10.1016/j.copbio.2025.103368
Dake Liu, Meng-Lun Hsieh, Yousong Ding
Human-associated microbes hold immense therapeutic potential, yet most species remain undomesticated due to cultivation barriers and limited genetic tools. Recent advances in genetic engineering are overcoming these challenges, enabling the precise manipulation of both domesticated and previously intractable microbes. This review highlights established strategies for engineering domesticated strains, such as Escherichia coli Nissle 1917 and lactic acid bacteria, for diverse therapeutic applications. We also discuss emerging tools, including optimized transformation protocols for skin commensals and genome-editing approaches for Clostridium species and undomesticated E. coli, that address key barriers in non-model microbes and expand the potential of engineered microbiome therapeutics.
与人类相关的微生物具有巨大的治疗潜力,但由于培养障碍和遗传工具有限,大多数物种仍未被驯化。基因工程的最新进展正在克服这些挑战,能够精确地操纵驯化和以前难以驾驭的微生物。本文综述了工程驯化菌株的建立策略,如大肠杆菌尼氏1917和乳酸菌,用于不同的治疗应用。我们还讨论了新兴工具,包括针对皮肤共生菌的优化转化方案和针对梭状芽胞杆菌和未驯化的大肠杆菌的基因组编辑方法,这些工具解决了非模式微生物中的关键障碍,并扩大了工程微生物组治疗的潜力。
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引用次数: 0
Engineering microbial exopolysaccharides for food applications. 食品用工程微生物胞外多糖。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1016/j.copbio.2025.103339
Jannis Broeker, Jochen Schmid

Microbial exopolysaccharides for direct food applications remain rare due to significant financial and regulatory hurdles. However, exopolysaccharides without direct food approval have recently been employed in various indirect food-related uses. This review highlights microbial exopolysaccharides with strong potential for both direct and indirect food applications and outlines engineering strategies to optimize their biotechnological production. For sucrase-based polysaccharides, enzyme engineering aimed at controlling molecular weight has shown strong potential for generating novel functional properties. In the case of synthase-based polysaccharides, leveraging epimerases or exploiting the natural promiscuity of the synthase enzyme emerges as a particularly promising approach. For heteropolysaccharides, this review presents some rare examples of successful engineering and heterologous expression in chassis organisms, while also identifying key challenges that still limit efficient optimization.

微生物胞外多糖的直接食品应用仍然很少,由于重大的财政和监管障碍。然而,未经直接食品批准的外多糖最近被用于各种间接食品相关用途。本文综述了具有直接和间接食品应用潜力的微生物外多糖,并概述了优化其生物技术生产的工程策略。对于蔗糖基多糖,旨在控制分子量的酶工程已经显示出产生新的功能特性的强大潜力。在以合酶为基础的多糖的情况下,利用外链酶或利用合酶的自然乱交成为一种特别有前途的方法。对于杂多糖,本文介绍了一些罕见的成功工程和在底盘生物中异源表达的例子,同时也指出了限制有效优化的关键挑战。
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引用次数: 0
Unveiling the prebiotic potential of polyphenols in gut health and metabolism. 揭示多酚在肠道健康和代谢中的益生元潜力。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1016/j.copbio.2025.103338
Katherine Petersen, Thomas J Mansell

Polyphenols are a diverse class of plant metabolites with noted health benefits, such as antioxidant, anticancer, and antidiabetic effects. Recently, these compounds have gained interest for their ability to manipulate the composition of the human gut microbiome through distinct mechanisms, including microbial metabolism, enzymatic biotransformation, and antimicrobial effects. For example, many gut microbes express β-glucosidases or polyphenol catabolizing enzymes (PAZymes), which could enable the use of these compounds in competitive niches. This review explores recent research on the enzymes that interact with these substrates, the mechanisms by which polyphenols modulate the gut microbiome, and the use of polyphenolic compounds as next-generation prebiotics for the benefit of the human host.

多酚是一类多种多样的植物代谢物,具有显著的健康益处,如抗氧化、抗癌和抗糖尿病作用。最近,这些化合物因其通过不同的机制(包括微生物代谢、酶促生物转化和抗菌作用)操纵人体肠道微生物组组成的能力而引起了人们的兴趣。例如,许多肠道微生物表达β-葡萄糖苷酶或多酚分解代谢酶(PAZymes),这可以使这些化合物在竞争激烈的生态位中使用。本文综述了与这些底物相互作用的酶的最新研究,多酚调节肠道微生物群的机制,以及多酚化合物作为造福人类宿主的下一代益生元的应用。
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引用次数: 0
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Current opinion in biotechnology
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