Pub Date : 2024-10-21DOI: 10.1016/j.copbio.2024.103216
Savannah E Butler , Margaret E Ackerman
Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for in vivo efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.
目前正在开发新型嵌合抗原受体（CAR）T细胞设计，以克服肿瘤识别、贩运、靶上但非肿瘤结合、细胞毒性、持久性以及肿瘤微环境中的免疫抑制等难题。传统的 CAR 工程是一个迭代、假设驱动的过程，在这个过程中，新的设计被合理地构建并测试体内疗效，我们借鉴了基于小分子和蛋白质的治疗发现领域的经验，同时考虑了高通量功能筛选技术如何开始应用于开发有前景的 CAR 候选者。我们回顾了高通量筛选方法的开发是如何简化 CAR 发现过程，最终提高效率和临床疗效的。
{"title":"Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery","authors":"Savannah E Butler , Margaret E Ackerman","doi":"10.1016/j.copbio.2024.103216","DOIUrl":"10.1016/j.copbio.2024.103216","url":null,"abstract":"<div><div>Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for <em>in vivo</em> efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103216"},"PeriodicalIF":7.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.copbio.2024.103213
Kshitija Shah , Soham Ray , Himadri Bose , Vijaya Pandey , James A Wohlschlegel , Shaily Mahendra
As anthropogenic activities continue to introduce various contaminants into the environment, the need for effective monitoring and bioremediation strategies is critical. Fungi, with their diverse enzymatic arsenal, offer promising solutions for the biotransformation of many pollutants. While conventional research reports on ligninolytic, oxidoreductive, and cytochrome P450 (CYP) enzymes, the vast potential of fungi, with approximately 10 345 protein sequences per species, remains largely untapped. This review describes recent advancements in fungal proteomics instruments as well as software and highlights their detoxification mechanisms and biochemical pathways. Additionally, it highlights lesser-known fungal enzymes with potential applications in environmental biotechnology. By reviewing the benefits and challenges associated with proteomics tools, we hope to summarize and promote the studies of fungi and fungal proteins relevant in the environment.
{"title":"Proteomics insights into the fungal-mediated bioremediation of environmental contaminants","authors":"Kshitija Shah , Soham Ray , Himadri Bose , Vijaya Pandey , James A Wohlschlegel , Shaily Mahendra","doi":"10.1016/j.copbio.2024.103213","DOIUrl":"10.1016/j.copbio.2024.103213","url":null,"abstract":"<div><div>As anthropogenic activities continue to introduce various contaminants into the environment, the need for effective monitoring and bioremediation strategies is critical. Fungi, with their diverse enzymatic arsenal, offer promising solutions for the biotransformation of many pollutants. While conventional research reports on ligninolytic, oxidoreductive, and cytochrome P450 (CYP) enzymes, the vast potential of fungi, with approximately 10 345 protein sequences per species, remains largely untapped. This review describes recent advancements in fungal proteomics instruments as well as software and highlights their detoxification mechanisms and biochemical pathways. Additionally, it highlights lesser-known fungal enzymes with potential applications in environmental biotechnology. By reviewing the benefits and challenges associated with proteomics tools, we hope to summarize and promote the studies of fungi and fungal proteins relevant in the environment.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103213"},"PeriodicalIF":7.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1016/j.copbio.2024.103210
Justin N Tan , Keshav Ratra , Steven W Singer , Blake A Simmons , Shubhasish Goswami , Deepika Awasthi
With the continuous increase in the world population, anthropogenic activities will generate more waste and create greenhouse gases such as methane, amplifying global warming. The biological conversion of methane into biochemicals is a sustainable solution to sequester and convert this greenhouse gas. Methanotrophic bacteria fulfill this role by utilizing methane as a feedstock while manufacturing various bioproducts. Recently, methanotrophs have made their mark in industrial biomanufacturing. However, unlike glucose-utilizing model organisms such as Escherichia coli and Saccharomyces cerevisiae, methanotrophs do not have established transformation methods and genetic tools, making these organisms challenging to engineer. Despite these challenges, recent advancements in methanotroph engineering demonstrate great promise, showcasing these C1-carbon-utilizing microbes as prospective hosts for bioproduction. This review discusses the recent developments and challenges in strain engineering, biomolecule production, and process development methodologies in the methanotroph field.
{"title":"Methane to bioproducts: unraveling the potential of methanotrophs for biomanufacturing","authors":"Justin N Tan , Keshav Ratra , Steven W Singer , Blake A Simmons , Shubhasish Goswami , Deepika Awasthi","doi":"10.1016/j.copbio.2024.103210","DOIUrl":"10.1016/j.copbio.2024.103210","url":null,"abstract":"<div><div>With the continuous increase in the world population, anthropogenic activities will generate more waste and create greenhouse gases such as methane, amplifying global warming. The biological conversion of methane into biochemicals is a sustainable solution to sequester and convert this greenhouse gas. Methanotrophic bacteria fulfill this role by utilizing methane as a feedstock while manufacturing various bioproducts. Recently, methanotrophs have made their mark in industrial biomanufacturing. However, unlike glucose-utilizing model organisms such as <em>Escherichia coli</em> and <em>Saccharomyces cerevisiae</em>, methanotrophs do not have established transformation methods and genetic tools, making these organisms challenging to engineer. Despite these challenges, recent advancements in methanotroph engineering demonstrate great promise, showcasing these C1-carbon-utilizing microbes as prospective hosts for bioproduction. This review discusses the recent developments and challenges in strain engineering, biomolecule production, and process development methodologies in the methanotroph field.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103210"},"PeriodicalIF":7.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.copbio.2024.103212
Karel Olavarria , Diana Z Sousa
Modern biotechnology requires the integration of several disciplines, with thermodynamics being a crucial one. Experimental approaches frequently used in biotechnology, such as rewiring of metabolic networks or culturing of micro-organisms in engineered environments, can benefit from the application of thermodynamic tools. In this paper, we provide an overview of several thermodynamic tools that are useful for the design and optimization of biotechnological processes, and we demonstrate their potential application in the production of poly-(3-hydroxybutyrate) (PHB) from carbon monoxide (CO). We discuss how these tools can aid in the design of metabolic engineering strategies, the calculation of expected yields, the assessment of the thermodynamic feasibility of the targeted conversions, the identification of potential thermodynamic bottlenecks, and the selection of genetic engineering targets. Although we illustrate these tools using the specific example of PHB production from CO, they can be applied to other substrates and products.
现代生物技术需要整合多个学科，其中热力学是一个重要学科。生物技术中经常使用的实验方法，如重新连接代谢网络或在工程环境中培养微生物，都可以从热力学工具的应用中获益。本文概述了几种有助于设计和优化生物技术过程的热力学工具，并展示了这些工具在利用一氧化碳（CO）生产聚-（3-羟基丁酸）（PHB）过程中的潜在应用。我们讨论了这些工具如何帮助设计代谢工程策略、计算预期产量、评估目标转化的热力学可行性、识别潜在的热力学瓶颈以及选择基因工程目标。虽然我们使用从 CO 生产 PHB 的具体实例来说明这些工具，但它们也可应用于其他底物和产品。
{"title":"Thermodynamic tools for more efficient biotechnological processes: an example in poly-(3-hydroxybutyrate) production from carbon monoxide","authors":"Karel Olavarria , Diana Z Sousa","doi":"10.1016/j.copbio.2024.103212","DOIUrl":"10.1016/j.copbio.2024.103212","url":null,"abstract":"<div><div>Modern biotechnology requires the integration of several disciplines, with thermodynamics being a crucial one. Experimental approaches frequently used in biotechnology, such as rewiring of metabolic networks or culturing of micro-organisms in engineered environments, can benefit from the application of thermodynamic tools. In this paper, we provide an overview of several thermodynamic tools that are useful for the design and optimization of biotechnological processes, and we demonstrate their potential application in the production of poly-(3-hydroxybutyrate) (PHB) from carbon monoxide (CO). We discuss how these tools can aid in the design of metabolic engineering strategies, the calculation of expected yields, the assessment of the thermodynamic feasibility of the targeted conversions, the identification of potential thermodynamic bottlenecks, and the selection of genetic engineering targets. Although we illustrate these tools using the specific example of PHB production from CO, they can be applied to other substrates and products.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103212"},"PeriodicalIF":7.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-28DOI: 10.1016/j.copbio.2024.103215
Tomohisa Hasunuma , Yong-Su Jin
{"title":"Editorial overview: Chemical biotechnology paving the way for a sustainable future","authors":"Tomohisa Hasunuma , Yong-Su Jin","doi":"10.1016/j.copbio.2024.103215","DOIUrl":"10.1016/j.copbio.2024.103215","url":null,"abstract":"","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103215"},"PeriodicalIF":7.1,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.copbio.2024.103209
Anna Joëlle Ruff
The phosphorus shortage is an unavoidable challenge that requires strategies to replace phosphorus sourced from ores. Food industry by-products are an unscoped resource for sustainable phosphorus recovery. Recent advances include biotechnological phosphorus upcycling from phytate-rich plant residues to polyphosphate as a food additive. The valorization of by-products such as deoiled seeds or brans additionally provides low-phosphorus feed and thereby minimizes the environmental burden. Phytate reduction in a cereal-rich diet by adding enzyme formulation is a further strategy that limits its antinutritive effect. However, sustainable P-management depends on phytases that have been customized and enhanced for thermostability and specific activity. The circular phosphorus economy is driven by emerging value chains and maturing phosphorus recovery technologies for market entry.
{"title":"Food industry side streams: an unexploited source for biotechnological phosphorus upcycling","authors":"Anna Joëlle Ruff","doi":"10.1016/j.copbio.2024.103209","DOIUrl":"10.1016/j.copbio.2024.103209","url":null,"abstract":"<div><div>The phosphorus shortage is an unavoidable challenge that requires strategies to replace phosphorus sourced from ores. Food industry by-products are an unscoped resource for sustainable phosphorus recovery. Recent advances include biotechnological phosphorus upcycling from phytate-rich plant residues to polyphosphate as a food additive. The valorization of by-products such as deoiled seeds or brans additionally provides low-phosphorus feed and thereby minimizes the environmental burden. Phytate reduction in a cereal-rich diet by adding enzyme formulation is a further strategy that limits its antinutritive effect. However, sustainable P-management depends on phytases that have been customized and enhanced for thermostability and specific activity. The circular phosphorus economy is driven by emerging value chains and maturing phosphorus recovery technologies for market entry.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103209"},"PeriodicalIF":7.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.copbio.2024.103208
Giuliano A Kullik , Moritz Waldmann , Thomas Renné
Polyphosphates play a crucial role in various biological processes, such as blood coagulation, energy homeostasis, and cellular stress response. However, their isolation, detection, and quantification present significant challenges. These difficulties arise primarily from their solubility, low concentration in mammals, and structural similarity to other ubiquitous biopolymers. This review provides an overview of the current understanding of polyphosphates in mammals, including their proposed functions and tissue distribution. It also examines key isolation techniques, such as chromatography and precipitation, alongside detection methods, such as colorimetric assays and enzymatic digestion. The strengths and limitations of these methods are discussed, as well as the challenges in preserving polyphosphate integrity. Recent advancements in isolation and detection are also highlighted, offering a comprehensive perspective essential for advancing polyphosphate research.
{"title":"Analysis of polyphosphate in mammalian cells and tissues: methods, functions and challenges","authors":"Giuliano A Kullik , Moritz Waldmann , Thomas Renné","doi":"10.1016/j.copbio.2024.103208","DOIUrl":"10.1016/j.copbio.2024.103208","url":null,"abstract":"<div><div>Polyphosphates play a crucial role in various biological processes, such as blood coagulation, energy homeostasis, and cellular stress response. However, their isolation, detection, and quantification present significant challenges. These difficulties arise primarily from their solubility, low concentration in mammals, and structural similarity to other ubiquitous biopolymers. This review provides an overview of the current understanding of polyphosphates in mammals, including their proposed functions and tissue distribution. It also examines key isolation techniques, such as chromatography and precipitation, alongside detection methods, such as colorimetric assays and enzymatic digestion. The strengths and limitations of these methods are discussed, as well as the challenges in preserving polyphosphate integrity. Recent advancements in isolation and detection are also highlighted, offering a comprehensive perspective essential for advancing polyphosphate research.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103208"},"PeriodicalIF":7.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0958166924001447/pdfft?md5=17966ef883b67a95df4e8997f1d363ab&pid=1-s2.0-S0958166924001447-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.copbio.2024.103207
Maxence Plouviez , Nicola Brown
Phosphorus (P) must continuously be added to soils as it is lost in the food chain and via leaching. Unfortunately, the mining and import of P to produce fertiliser is unsustainable and costly. Potential solutions to the global issues of P rock depletion and pollution lie in microalgae and cyanobacteria. With an ability to intracellularly store P as polyphosphates, microalgae and cyanobacteria could provide the basis for removing P from water streams, thereby mitigating eutrophication, and even enabling P recovery as P-rich biomass. Metabolic engineering or changes in growing conditions have been demonstrated to improve P removal and recovery by triggering polyphosphates synthesis in the laboratory. This now needs to be replicated at full scale.
{"title":"Polyphosphate accumulation in microalgae and cyanobacteria: recent advances and opportunities for phosphorus upcycling","authors":"Maxence Plouviez , Nicola Brown","doi":"10.1016/j.copbio.2024.103207","DOIUrl":"10.1016/j.copbio.2024.103207","url":null,"abstract":"<div><p>Phosphorus (P) must continuously be added to soils as it is lost in the food chain and via leaching. Unfortunately, the mining and import of P to produce fertiliser is unsustainable and costly. Potential solutions to the global issues of P rock depletion and pollution lie in microalgae and cyanobacteria. With an ability to intracellularly store P as polyphosphates, microalgae and cyanobacteria could provide the basis for removing P from water streams, thereby mitigating eutrophication, and even enabling P recovery as P-rich biomass. Metabolic engineering or changes in growing conditions have been demonstrated to improve P removal and recovery by triggering polyphosphates synthesis in the laboratory. This now needs to be replicated at full scale.</p></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103207"},"PeriodicalIF":7.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0958166924001435/pdfft?md5=3173f077931b3bf311c27c5712c4e495&pid=1-s2.0-S0958166924001435-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.copbio.2024.103197
James J Elser , Douglas F Call , Jessica A Deaver , Owen W Duckworth , Brooke K Mayer , Eric McLamore , Bruce Rittmann , Maheen Mahmood , Paul Westerhoff
Phosphorus (P) is essential for growing crops, but the supply of high-quality phosphate rock reserves used for fertilizer production is finite while losses of P from the food/waste system cause considerable environmental damage. A variety of emerging approaches in biotechnology are reviewed that hold promise for improving the sustainability of P use in the food/water systems. These include improved sensors, cell culture approaches to meat production, bio-based P adsorption and transformation strategies, advancements in understanding of polyphosphate-accumulating organisms, and new approaches involving biomineralization and anaerobic treatment. By advancing these technologies to scale, progress can be made in developing a circular phosphorus economy that improves food security while protecting drinking water and aquatic ecosystems.
{"title":"The phosphorus challenge: biotechnology approaches for a sustainable phosphorus system","authors":"James J Elser , Douglas F Call , Jessica A Deaver , Owen W Duckworth , Brooke K Mayer , Eric McLamore , Bruce Rittmann , Maheen Mahmood , Paul Westerhoff","doi":"10.1016/j.copbio.2024.103197","DOIUrl":"10.1016/j.copbio.2024.103197","url":null,"abstract":"<div><p>Phosphorus (P) is essential for growing crops, but the supply of high-quality phosphate rock reserves used for fertilizer production is finite while losses of P from the food/waste system cause considerable environmental damage. A variety of emerging approaches in biotechnology are reviewed that hold promise for improving the sustainability of P use in the food/water systems. These include improved sensors, cell culture approaches to meat production, bio-based P adsorption and transformation strategies, advancements in understanding of polyphosphate-accumulating organisms, and new approaches involving biomineralization and anaerobic treatment. By advancing these technologies to scale, progress can be made in developing a circular phosphorus economy that improves food security while protecting drinking water and aquatic ecosystems.</p></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103197"},"PeriodicalIF":7.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0958166924001332/pdfft?md5=1e30f2e61cbd06c2d4ed6d3031498504&pid=1-s2.0-S0958166924001332-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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