Biotechnology advances最新文献

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Biosynthesis and bioactivities of triterpenoids from Centella asiatica: Challenges and opportunities

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-18 DOI: 10.1016/j.biotechadv.2025.108541

Weizhu Zeng , Hongbiao Li , Shike Liu , Zhengshan Luo , Jian Chen , Jingwen Zhou

Centella asiatica (L.) Urban is an herbaceous perennial plant that has long been widely used in traditional medicine, due to its diverse wound-healing, neuroprotection, antioxidant and anti-inflammatory properties. The major functional bioactive secondary metabolites are the triterpenoids asiatic acid, madecassic acid, asiaticoside and madecassoside, collectively known as centellosides. Current extraction methods for C. asiatica are unable to meet market demand for extracts and pure functional components. Biotechnological approaches based on synthetic biology and microbial cell factories are a promising alternative. This review summarises the major secondary metabolites and their biological activities, and the biosynthetic pathway of functional triterpenoids in C. asiatica. Biotechnological production of centellosides is also described, including in vitro plant cultures and construction of microbial cell factories. Finally, current challenges and future perspectives for sustainable production of centellosides are discussed, and guidelines for future engineering are proposed.

{"title":"Biosynthesis and bioactivities of triterpenoids from Centella asiatica: Challenges and opportunities","authors":"Weizhu Zeng , Hongbiao Li , Shike Liu , Zhengshan Luo , Jian Chen , Jingwen Zhou","doi":"10.1016/j.biotechadv.2025.108541","DOIUrl":"10.1016/j.biotechadv.2025.108541","url":null,"abstract":"<div><div><em>Centella asiatica</em> (L.) Urban is an herbaceous perennial plant that has long been widely used in traditional medicine, due to its diverse wound-healing, neuroprotection, antioxidant and anti-inflammatory properties. The major functional bioactive secondary metabolites are the triterpenoids asiatic acid, madecassic acid, asiaticoside and madecassoside, collectively known as centellosides. Current extraction methods for <em>C. asiatica</em> are unable to meet market demand for extracts and pure functional components. Biotechnological approaches based on synthetic biology and microbial cell factories are a promising alternative. This review summarises the major secondary metabolites and their biological activities, and the biosynthetic pathway of functional triterpenoids in <em>C. asiatica.</em> Biotechnological production of centellosides is also described, including <em>in vitro</em> plant cultures and construction of microbial cell factories. Finally, current challenges and future perspectives for sustainable production of centellosides are discussed, and guidelines for future engineering are proposed.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"80 ","pages":"Article 108541"},"PeriodicalIF":12.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454927","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

Alpha ketoacid decarboxylases: Diversity, structures, reaction mechanisms, and applications for biomanufacturing of platform chemicals and fuels.

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-13 DOI: 10.1016/j.biotechadv.2025.108531

Khanh Ha, Seunghyun Ryu, Cong T Trinh

In living cells, alpha ketoacid decarboxylases (KDCs, EC 4.1.1.-) are a class of enzymes that convert alpha ketoacids into aldehydes through decarboxylation. These aldehydes serve as either drop-in chemicals or precursors for the biosynthesis of alcohols, carboxylic acids, esters, and alkanes. These compounds play crucial roles in cellular metabolism and fitness and the bioeconomy, facilitating the sustainable and renewable biomanufacturing of platform chemicals and fuels. This review explores the diversity and classification of KDCs, detailing their structures, mechanisms, and functions. We highlight recent advancements in repurposing KDCs to enhance their efficiency and robustness for biomanufacturing. Additionally, we present modular KDC-dependent metabolic pathways for the microbial biosynthesis of aldehydes, alcohols, carboxylic acids, esters, and alkanes. Finally, we discuss recent development in the modular cell engineering technology that can be potentially applied to harness the diversity of KDC-dependent pathways for biomanufacturing platform chemicals and fuels.

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引用次数: 0

Chimeric enzymes in the pulp and paper making industry: Current developments

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-09 DOI: 10.1016/j.biotechadv.2025.108530

Abdullah Arsalan , Yuvaraj Ravikumar , Xinrui Tang , Zijing Cao , Mei Zhao , Wenjing Sun , Xianghui Qi

The pulp and paper (P&P) industry plays a vital role in supporting the social and economic progress of a country by supplying essential commodities. Conventional P&P processing often consumes significant energy and use chemical agents to produce hazardous intermediates. The use of enzymes in the P&P industry has significantly reduced both the chemical and energy demands during processing. A variety of enzyme combination cocktails are used to perform multiple functions in a single step, but often fail to operate synergistically because of significant differences in operational conditions. This lack of synergy under various operating conditions highlights the need for engineered chimeric enzymes. Moreover, enzyme engineering approaches enable enzymes to perform catalysis in sub-optimal environment. Enzymes have been engineered to improve their catalytic properties and enhance operational stability. Designing multifunctional or chimeric enzymes can function simultaneously across diverse operational conditions. Chimeric enzymes enable effective synergistic action of multiple enzymes in the P&P industry. This review aims to provide clear insights into the selective development of chimeric enzymes using enzyme engineering approaches for their effective use in the P&P industry.

{"title":"Chimeric enzymes in the pulp and paper making industry: Current developments","authors":"Abdullah Arsalan , Yuvaraj Ravikumar , Xinrui Tang , Zijing Cao , Mei Zhao , Wenjing Sun , Xianghui Qi","doi":"10.1016/j.biotechadv.2025.108530","DOIUrl":"10.1016/j.biotechadv.2025.108530","url":null,"abstract":"<div><div>The pulp and paper (P&P) industry plays a vital role in supporting the social and economic progress of a country by supplying essential commodities. Conventional P&P processing often consumes significant energy and use chemical agents to produce hazardous intermediates. The use of enzymes in the P&P industry has significantly reduced both the chemical and energy demands during processing. A variety of enzyme combination cocktails are used to perform multiple functions in a single step, but often fail to operate synergistically because of significant differences in operational conditions. This lack of synergy under various operating conditions highlights the need for engineered chimeric enzymes. Moreover, enzyme engineering approaches enable enzymes to perform catalysis in sub-optimal environment. Enzymes have been engineered to improve their catalytic properties and enhance operational stability. Designing multifunctional or chimeric enzymes can function simultaneously across diverse operational conditions. Chimeric enzymes enable effective synergistic action of multiple enzymes in the P&P industry. This review aims to provide clear insights into the selective development of chimeric enzymes using enzyme engineering approaches for their effective use in the P&P industry.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"79 ","pages":"Article 108530"},"PeriodicalIF":12.1,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395144","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

Post-translational assembly of multi-functional antibody

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-08 DOI: 10.1016/j.biotechadv.2025.108533

Baizhen Gao , Qing Sun

The advent of multi-specific antibodies has introduced a significant advantage over traditional monoclonal antibody therapeutics by engaging multiple targets and pathways. This review delves into the post-translational assembly techniques for multi-specific antibodies, highlighting the innovations and challenges associated with approaches of chemical conjugation, oligonucleotide-mediated assembly, and protein-protein interactions. Chemical conjugation methods have evolved to enhance the assembly process's specificity and flexibility, enabling transient engagement and versatile antibody formats. Meanwhile, oligonucleotide-mediated assembly leverages the precision of Watson–Crick base pairing, granting unmatched control over the antibody's structure and functional orientation. Additionally, protein-protein interaction strategies, notably through SpyTag/SpyCatcher systems, present a direct assembly approach without necessitating ancillary modifications, streamlining the production process. This review summarizes the significance of these methodologies in generating antibodies with diverse structures and multi-target engagement capabilities, underscoring their potential in improving therapeutic efficacy and reducing production complexity.

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引用次数: 0

Computational advances in biosynthetic gene cluster discovery and prediction

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-07 DOI: 10.1016/j.biotechadv.2025.108532

Sisi Zhu , Hongquan Xu , Yuhong Liu , Yanfeng Hong , Haowen Yang , Changli Zhou , Lin Tao

Biosynthetic gene clusters (BGCs) are groups of clustered genes found in bacteria, fungi, and some plants and animals that are crucial for synthesizing secondary metabolites. In recent years, genome mining of BGCs has emerged as a prominent research focus, particularly in natural product discovery and drug development. Compared to traditional experimental methods, applying computational techniques has significantly enhanced the efficiency of BGC identification and annotation, thereby facilitating the discovery of novel metabolites. The advent of artificial intelligence, particularly machine learning models and more advanced deep learning algorithms, has significantly enhanced both the speed and precision of BGC mining. This review offers a comprehensive introduction to currently developed BGC databases and prediction tools, highlighting the potential of machine learning technologies in BGC mining. Additionally, it summarizes the challenges computational methods face in this area and discusses future research directions.

生物合成基因簇（BGCs）是存在于细菌、真菌和一些动植物中的基因群，是合成次生代谢物的关键。近年来，BGCs 基因组挖掘已成为一个突出的研究重点，尤其是在天然产物发现和药物开发方面。与传统的实验方法相比，计算技术的应用大大提高了 BGC 鉴定和注释的效率，从而促进了新型代谢物的发现。人工智能的出现，特别是机器学习模型和更先进的深度学习算法，大大提高了BGC挖掘的速度和精度。这篇综述全面介绍了目前开发的 BGC 数据库和预测工具，强调了机器学习技术在 BGC 挖掘方面的潜力。此外，它还总结了计算方法在这一领域面临的挑战，并讨论了未来的研究方向。

引用次数: 0

Polyhydroxyalkanoates production from microalgae for sustainable bioplastics: A review

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-06 DOI: 10.1016/j.biotechadv.2025.108529

Syarifa Ilhami , Siti Nur Syaza Abdul Rahman , Muhammad Iqhrammullah , Zhafran Hamid , Yee Ho Chai , Man Kee Lam

Microalgae have emerged as a promising and sustainable source for polyhydroxyalkanoates (PHA), which are increasingly recognized for their potential in bioplastics production. However, the widespread application of microalgae-derived PHA faces challenges related to economic feasibility and scalability. This review provides a comprehensive analysis of recent advancements in the cultivation and optimization of microalgae for PHA production, highlighting the critical role of nutrient limitation, particularly nitrogen and phosphorus, in enhancing PHA accumulation. This review also explores the effectiveness of various cultivation systems, including autotrophic, heterotrophic, and mixotrophic approaches, in maximizing PHA yields. Environmental factors such as light intensity, salinity, and pH are examined for their influence on PHA synthesis pathways. Additionally, it identifies key technical and economic challenges that must be addressed to commercialize microalgae-based bioplastics to fully harness the potential of microalgae in sustainable bioplastic production.

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引用次数: 0

Heparin and heparin-like modifications in hemodialysis membranes: Current innovations and future directions

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-06 DOI: 10.1016/j.biotechadv.2025.108527

Putu Teta Prihartini Aryanti , Febrianto Adi Nugroho , Yudith Yunia Kusmala

Heparinized hemodialysis membranes represent a significant advancement in improving the biocompatibility and anticoagulant properties of dialysis treatments. This review explores the current challenges and innovations in developing these membranes, focusing on the incorporation of heparin and heparin-like substances to reduce protein adsorption, platelet adhesion, and clot formation. The methods for heparin immobilization, including covalent bonding, layer-by-layer assembly, and blending, offer promising results in enhancing membrane performance. However, issues such as long-term stability, large-scale production, and cost-effectiveness remain critical barriers to their widespread adoption. The review also highlights the role of surface activation techniques and nanotechnology in improving the functionality of heparinized membranes. Advanced methods like plasma treatment and polymer grafting provide better heparin attachment, while nanomaterial integration allows for improved blood compatibility and controlled heparin release. Despite these innovations, challenges such as heparin degradation, uneven coating, and the complexity of scaling up remain unresolved. Future research should focus on optimizing heparin distribution, enhancing durability, and making the production process more cost-efficient. This paper outlines potential interdisciplinary approaches, such as bioinspired materials and nanotechnology applications, to address these challenges and pave the way for next-generation hemodialysis membranes that are safer, more effective, and more accessible.

{"title":"Heparin and heparin-like modifications in hemodialysis membranes: Current innovations and future directions","authors":"Putu Teta Prihartini Aryanti , Febrianto Adi Nugroho , Yudith Yunia Kusmala","doi":"10.1016/j.biotechadv.2025.108527","DOIUrl":"10.1016/j.biotechadv.2025.108527","url":null,"abstract":"<div><div>Heparinized hemodialysis membranes represent a significant advancement in improving the biocompatibility and anticoagulant properties of dialysis treatments. This review explores the current challenges and innovations in developing these membranes, focusing on the incorporation of heparin and heparin-like substances to reduce protein adsorption, platelet adhesion, and clot formation. The methods for heparin immobilization, including covalent bonding, layer-by-layer assembly, and blending, offer promising results in enhancing membrane performance. However, issues such as long-term stability, large-scale production, and cost-effectiveness remain critical barriers to their widespread adoption. The review also highlights the role of surface activation techniques and nanotechnology in improving the functionality of heparinized membranes. Advanced methods like plasma treatment and polymer grafting provide better heparin attachment, while nanomaterial integration allows for improved blood compatibility and controlled heparin release. Despite these innovations, challenges such as heparin degradation, uneven coating, and the complexity of scaling up remain unresolved. Future research should focus on optimizing heparin distribution, enhancing durability, and making the production process more cost-efficient. This paper outlines potential interdisciplinary approaches, such as bioinspired materials and nanotechnology applications, to address these challenges and pave the way for next-generation hemodialysis membranes that are safer, more effective, and more accessible.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"80 ","pages":"Article 108527"},"PeriodicalIF":12.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373620","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

Unleashing the potential of microbial biosynthesis of monoterpenes via enzyme and metabolic engineering

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-05 DOI: 10.1016/j.biotechadv.2025.108525

Dianqi Yang , Hong Liang , Xuxu Li, Chenyu Zhang, Zewei Lu, Xiaoqiang Ma

Monoterpenes (MTPs) are valuable isoprenoids widely used in cosmetics, food flavorings, pharmaceuticals, etc. Compared to plant extraction and chemical synthesis, microbial biosynthesis offers superior sustainability and efficiency in producing natural MTPs, overcoming the limitations of raw material dependency, environmental impact, and racemic mixtures inherent in these methods. This review comprehensively discusses the development of natural or non-natural biosynthetic pathways for producing regular and irregular MTPs, emphasizing the importance of enzyme and metabolic engineering to optimize monoterpene synthases (MTPSs) in various engineered microbial cell factories (MCFs). The advances in functional expression of MTPS to enhance enzyme activity, substrate channeling of MTPS with critical biosynthesis enzymes, protein engineering of MTPS, targeted localization of MTPS in the subcellular organelle, and other favorable engineering strategies are discussed in detail. Leveraging these technologies, the engineered microbes will achieve the production of the defined product profile with higher titer/yield/productivity and improved industrial adaptability. Furthermore, we highlight the important development direction for optimizing MTPS performance and biosynthetic pathways, ensuring the microbial production of natural MTPs in a more efficient and application-specific manner.

{"title":"Unleashing the potential of microbial biosynthesis of monoterpenes via enzyme and metabolic engineering","authors":"Dianqi Yang , Hong Liang , Xuxu Li, Chenyu Zhang, Zewei Lu, Xiaoqiang Ma","doi":"10.1016/j.biotechadv.2025.108525","DOIUrl":"10.1016/j.biotechadv.2025.108525","url":null,"abstract":"<div><div>Monoterpenes (MTPs) are valuable isoprenoids widely used in cosmetics, food flavorings, pharmaceuticals, etc. Compared to plant extraction and chemical synthesis, microbial biosynthesis offers superior sustainability and efficiency in producing natural MTPs, overcoming the limitations of raw material dependency, environmental impact, and racemic mixtures inherent in these methods. This review comprehensively discusses the development of natural or non-natural biosynthetic pathways for producing regular and irregular MTPs, emphasizing the importance of enzyme and metabolic engineering to optimize monoterpene synthases (MTPSs) in various engineered microbial cell factories (MCFs). The advances in functional expression of MTPS to enhance enzyme activity, substrate channeling of MTPS with critical biosynthesis enzymes, protein engineering of MTPS, targeted localization of MTPS in the subcellular organelle, and other favorable engineering strategies are discussed in detail. Leveraging these technologies, the engineered microbes will achieve the production of the defined product profile with higher titer/yield/productivity and improved industrial adaptability. Furthermore, we highlight the important development direction for optimizing MTPS performance and biosynthetic pathways, ensuring the microbial production of natural MTPs in a more efficient and application-specific manner.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"79 ","pages":"Article 108525"},"PeriodicalIF":12.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373637","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

Unlocking the full potential of plant cell-based production for valuable proteins: Challenges and innovative strategies

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-04 DOI: 10.1016/j.biotechadv.2025.108526

Jianfeng Xu , Paula PerezSanchez , Shekoofeh Sadravi

Plant cell-based bioproduction systems offer a promising platform for the sustainable production of valuable proteins as they provide distinctive advantages over mammalian cell culture and whole plant cultivation. However, significant technical challenges remain, including low productivity, altered efficacy of plant-derived proteins, along with issues in culture process development, such as cell clumping, genetic instability, and difficulties with cryopreservation. To date, the full production potential of this platform remains largely untapped. This review addresses these critical challenges and proposes innovative strategies to unlock the full potential of the production platform. Rather than simply revisiting past advancements or summarizing current progress, it proposes forward-thinking solutions with a particular emphasis on cellular engineering. Key strategies include designing novel protein partners to enhance recombinant protein accumulation and functionality, employing precise gene integration techniques in genome to enhance transgene transcription, implementing cutting-edge methods for screening and maintaining elite cell lines to mitigate genetic instability, and leveraging genome editing tools for cellular engineering to develop new plant cell lines optimized for bioproduction. A key focus is on cell wall engineering to develop cellulose- or pectin-deficient cell lines, facilitating modifications to the morphology of existing plant cell lines. By exploring these innovative approaches, this review aims to foster innovative thinking and inspire future research in plant cell-based bioproduction.

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引用次数: 0

Cellular variability as a driver for bioprocess innovation and optimization

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2025-02-04 DOI: 10.1016/j.biotechadv.2025.108528

M. Eigenfeld , S.P. Schwaminger

Cellular heterogeneity plays a crucial role in biotechnological processes, significantly influencing metabolic activity, product yield, and process consistency. This review explores the different dimensions of cellular heterogeneity, focusing on its manifestation at both single-cell and population levels. The study examines how factors such as asymmetric cell division, age, and environmental conditions contribute to functional diversity within cell populations, with an emphasis on microorganisms like yeast. Age-related cellular heterogeneity, in particular, is highlighted for its impact on metabolic pathways, mitochondrial function, and secondary metabolite production, which directly affect bioprocess outcomes. Furthermore, the review discusses advanced techniques for detecting and managing heterogeneity, including surface marker-based approaches, which utilize proteins, polysaccharides, and lipids, and label-free methods that leverage cellular volume and physical properties for separation. Understanding and controlling cellular heterogeneity is essential for optimizing industrial bioprocesses, improving yield, and ensuring product quality. The review also underscores the potential of emerging biotechnological tools, such as real-time single-cell analysis and microfluidic devices, in enhancing separation techniques and managing cellular diversity for better process efficiency and robustness.

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