Pub Date : 2024-11-20DOI: 10.1016/j.biotechadv.2024.108479
Yuhan Zhang , Jianxiao Zhao , Xi Sun , Yangyang Zheng , Tao Chen , Zhiwen Wang
Transcriptional regulatory networks (TRNs) play a crucial role in exploring microbial life activities and complex regulatory mechanisms. The comprehensive reconstruction of TRNs requires the integration of large-scale experimental data, which poses significant challenges due to the complexity of regulatory relationships. The application of machine learning tools, such as clustering analysis, has been employed to investigate TRNs, but these methods have limitations in capturing both global and local co-expression effects. In contrast, Independent Component Analysis (ICA) has emerged as a powerful analysis algorithm for modularizing independently regulated gene sets in TRNs, allowing it to account for both global and local co-expression effects. In this review, we comprehensively summarize the application of ICA in unraveling TRNs and highlight the research progress in three key aspects: (1) extending TRNs with iModulon analysis; (2) elucidating the regulatory mechanisms triggered by environmental perturbation; and (3) exploring the mechanisms of transcriptional regulation triggered by changes in microbial physiological state. At the end of this review, we also address the challenges facing ICA in TRN analysis and outline future research directions to promote the advancement of ICA-based transcriptomics analysis in biotechnology and related fields.
{"title":"Leveraging independent component analysis to unravel transcriptional regulatory networks: A critical review and future directions","authors":"Yuhan Zhang , Jianxiao Zhao , Xi Sun , Yangyang Zheng , Tao Chen , Zhiwen Wang","doi":"10.1016/j.biotechadv.2024.108479","DOIUrl":"10.1016/j.biotechadv.2024.108479","url":null,"abstract":"<div><div>Transcriptional regulatory networks (TRNs) play a crucial role in exploring microbial life activities and complex regulatory mechanisms. The comprehensive reconstruction of TRNs requires the integration of large-scale experimental data, which poses significant challenges due to the complexity of regulatory relationships. The application of machine learning tools, such as clustering analysis, has been employed to investigate TRNs, but these methods have limitations in capturing both global and local co-expression effects. In contrast, Independent Component Analysis (ICA) has emerged as a powerful analysis algorithm for modularizing independently regulated gene sets in TRNs, allowing it to account for both global and local co-expression effects. In this review, we comprehensively summarize the application of ICA in unraveling TRNs and highlight the research progress in three key aspects: (1) extending TRNs with iModulon analysis; (2) elucidating the regulatory mechanisms triggered by environmental perturbation; and (3) exploring the mechanisms of transcriptional regulation triggered by changes in microbial physiological state. At the end of this review, we also address the challenges facing ICA in TRN analysis and outline future research directions to promote the advancement of ICA-based transcriptomics analysis in biotechnology and related fields.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108479"},"PeriodicalIF":12.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692671","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}
Pub Date : 2024-11-19DOI: 10.1016/j.biotechadv.2024.108480
Hossein Kavoni , Iman Shahidi Pour Savizi , Nathan E. Lewis , Seyed Abbas Shojaosadati
The production of monoclonal antibodies (mAbs) using Chinese Hamster Ovary (CHO) cells has revolutionized the treatment of numerous diseases, solidifying their position as a cornerstone of the biopharmaceutical industry. However, achieving maximum mAb production while upholding strict product quality standards remains a significant hurdle. Optimizing cell culture media emerges as a critical factor in this endeavor, requiring a nuanced understanding of the complex interplay of nutrients, growth factors, and other components that profoundly influence cellular growth, productivity, and product quality. Significant strides have been made in media optimization, including techniques such as media blending, one factor at a time, and statistical design of experiments approaches. The present review provides a comprehensive analysis of the recent advancements in culture media design strategies, focusing on the comparative application of systems biology (SB) and machine learning (ML) approaches. The applications of SB and ML in optimizing CHO cell culture medium and successful examples of their use are summarized. Finally, we highlight the immense potential of integrating SB and ML, emphasizing the development of hybrid models that leverage the strengths of both approaches for robust, efficient, and scalable optimization of mAb production in CHO cells. This review provides a roadmap for researchers and industry professionals to navigate the complex landscape of mAb production optimization, paving the way for developing next-generation CHO cell culture media that drive significant improvements in yield and productivity.
利用中国仓鼠卵巢（CHO）细胞生产单克隆抗体（mAb）为众多疾病的治疗带来了革命性的变化，巩固了其作为生物制药行业基石的地位。然而，如何在保证严格的产品质量标准的同时实现最大的 mAb 产量仍然是一个重大障碍。优化细胞培养基是这一努力的关键因素，需要对营养物质、生长因子和其他成分的复杂相互作用有细致入微的了解，这些成分对细胞生长、生产率和产品质量有着深远的影响。在培养基优化方面已经取得了长足的进步，包括培养基混合、一次一个因子和统计实验设计方法等技术。本综述全面分析了培养基设计策略的最新进展，重点是系统生物学（SB）和机器学习（ML）方法的比较应用。综述了系统生物学（SB）和机器学习（ML）方法在优化 CHO 细胞培养基方面的应用及其成功案例。最后，我们强调了整合 SB 和 ML 的巨大潜力，强调开发混合模型，利用两种方法的优势，稳健、高效、可扩展地优化 CHO 细胞中 mAb 的生产。这篇综述为研究人员和业界专业人士提供了一个路线图，帮助他们驾驭 mAb 生产优化的复杂局面，为开发新一代 CHO 细胞培养基铺平道路，从而显著提高产量和生产率。
{"title":"Recent advances in culture medium design for enhanced production of monoclonal antibodies in CHO cells: A comparative study of machine learning and systems biology approaches","authors":"Hossein Kavoni , Iman Shahidi Pour Savizi , Nathan E. Lewis , Seyed Abbas Shojaosadati","doi":"10.1016/j.biotechadv.2024.108480","DOIUrl":"10.1016/j.biotechadv.2024.108480","url":null,"abstract":"<div><div>The production of monoclonal antibodies (mAbs) using Chinese Hamster Ovary (CHO) cells has revolutionized the treatment of numerous diseases, solidifying their position as a cornerstone of the biopharmaceutical industry. However, achieving maximum mAb production while upholding strict product quality standards remains a significant hurdle. Optimizing cell culture media emerges as a critical factor in this endeavor, requiring a nuanced understanding of the complex interplay of nutrients, growth factors, and other components that profoundly influence cellular growth, productivity, and product quality. Significant strides have been made in media optimization, including techniques such as media blending, one factor at a time, and statistical design of experiments approaches. The present review provides a comprehensive analysis of the recent advancements in culture media design strategies, focusing on the comparative application of systems biology (SB) and machine learning (ML) approaches. The applications of SB and ML in optimizing CHO cell culture medium and successful examples of their use are summarized. Finally, we highlight the immense potential of integrating SB and ML, emphasizing the development of hybrid models that leverage the strengths of both approaches for robust, efficient, and scalable optimization of mAb production in CHO cells. This review provides a roadmap for researchers and industry professionals to navigate the complex landscape of mAb production optimization, paving the way for developing next-generation CHO cell culture media that drive significant improvements in yield and productivity.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108480"},"PeriodicalIF":12.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685908","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}
Pub Date : 2024-11-17DOI: 10.1016/j.biotechadv.2024.108478
Ya-Jun Liu , Xiaoqing Wang , Yuman Sun , Yingang Feng
In bacteria, where gene transcription and translation occur concurrently, post-transcriptional regulation is acknowledged to be effective and precise. The 5′ untranslated regions (5′ UTRs) typically harbor diverse post-transcriptional regulatory elements, like riboswitches, RNA thermometers, small RNAs, and upstream open reading frames, that serve to modulate transcription termination, translation initiation, and mRNA stability. Consequently, exploring 5′ UTR-derived regulatory elements is vital for synthetic biology and metabolic engineering. Over the past few years, the investigation of successive mechanisms has facilitated the development of various genetic tools from bacterial 5′ UTRs. This review consolidates current understanding of 5′ UTR regulatory functions, presents recent progress in 5′ UTR-element design and screening, updates the tools and regulatory strategies developed, and highlights the challenges and necessity of establishing reliable bioinformatic analysis methods and non-model bacterial chassis in the future.
{"title":"Bacterial 5′ UTR: A treasure-trove for post-transcriptional regulation","authors":"Ya-Jun Liu , Xiaoqing Wang , Yuman Sun , Yingang Feng","doi":"10.1016/j.biotechadv.2024.108478","DOIUrl":"10.1016/j.biotechadv.2024.108478","url":null,"abstract":"<div><div>In bacteria, where gene transcription and translation occur concurrently, post-transcriptional regulation is acknowledged to be effective and precise. The 5′ untranslated regions (5′ UTRs) typically harbor diverse post-transcriptional regulatory elements, like riboswitches, RNA thermometers, small RNAs, and upstream open reading frames, that serve to modulate transcription termination, translation initiation, and mRNA stability. Consequently, exploring 5′ UTR-derived regulatory elements is vital for synthetic biology and metabolic engineering. Over the past few years, the investigation of successive mechanisms has facilitated the development of various genetic tools from bacterial 5′ UTRs. This review consolidates current understanding of 5′ UTR regulatory functions, presents recent progress in 5′ UTR-element design and screening, updates the tools and regulatory strategies developed, and highlights the challenges and necessity of establishing reliable bioinformatic analysis methods and non-model bacterial chassis in the future.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108478"},"PeriodicalIF":12.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646927","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}
Pub Date : 2024-11-16DOI: 10.1016/j.biotechadv.2024.108477
Linyue Tian , Tianqi Qi , Fenghui Zhang , Vinh G. Tran , Jifeng Yuan , Yuanpeng Wang , Ning He , Mingfeng Cao
Increasing attention is being focused on using lignocellulose for valuable products. Microbial decomposition can convert lignocellulose into renewable biofuels and other high-value bioproducts, contributing to sustainable development. However, the presence of inhibitors in lignocellulosic hydrolysates can negatively affect microorganisms during fermentation. Improving microbial tolerance to these hydrolysates is a major focus in metabolic engineering. Traditional detoxification methods increase costs, so there is a need for cheap and efficient cell-based detoxification strategies. Synthetic biology approaches offer several strategies for improving microbial tolerance, including redox balancing, membrane engineering, omics-guided technologies, expression of protectants and transcription factors, irrational engineering, cell flocculation, and other novel technologies. Advances in molecular biology, high-throughput sequencing, and artificial intelligence (AI) allow for precise strain modification and efficient industrial production. Developing AI-based computational models to guide synthetic biology efforts and creating large-scale heterologous libraries with automation and high-throughput technologies will be important for future research.
{"title":"Synthetic biology approaches to improve tolerance of inhibitors in lignocellulosic hydrolysates","authors":"Linyue Tian , Tianqi Qi , Fenghui Zhang , Vinh G. Tran , Jifeng Yuan , Yuanpeng Wang , Ning He , Mingfeng Cao","doi":"10.1016/j.biotechadv.2024.108477","DOIUrl":"10.1016/j.biotechadv.2024.108477","url":null,"abstract":"<div><div>Increasing attention is being focused on using lignocellulose for valuable products. Microbial decomposition can convert lignocellulose into renewable biofuels and other high-value bioproducts, contributing to sustainable development. However, the presence of inhibitors in lignocellulosic hydrolysates can negatively affect microorganisms during fermentation. Improving microbial tolerance to these hydrolysates is a major focus in metabolic engineering. Traditional detoxification methods increase costs, so there is a need for cheap and efficient cell-based detoxification strategies. Synthetic biology approaches offer several strategies for improving microbial tolerance, including redox balancing, membrane engineering, omics-guided technologies, expression of protectants and transcription factors, irrational engineering, cell flocculation, and other novel technologies. Advances in molecular biology, high-throughput sequencing, and artificial intelligence (AI) allow for precise strain modification and efficient industrial production. Developing AI-based computational models to guide synthetic biology efforts and creating large-scale heterologous libraries with automation and high-throughput technologies will be important for future research.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108477"},"PeriodicalIF":12.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646932","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}
Pub Date : 2024-11-12DOI: 10.1016/j.biotechadv.2024.108476
Carmen Sánchez
Fusarium is genetically diverse and widely distributed geographically. It is one of the genera with more endophytes (which cause no damage to the host plants). This review highlights the capability of Fusarium species to degrade environmental pollutants and describes the biodegradation pathways of some of the emerging environmental contaminants. Some Fusarium species use metabolic strategies enabling them to efficiently mineralize high concentrations of toxic environmental pollutants. These fungi can degrade hydrocarbons, pesticides, herbicides, dyes, pharmaceutical compounds, explosives, plastics, and plastic additives, among other pollutants, and possess high metal biosorption capabilities. According to data from consulted reports, Fusarium strains showed a percentage of biodegradation of a variety of contaminants ranging between 30 % and 100 % for different tested concentrations (from 1 mg to 10 g/L) in a time range between 10 h and 90 d. Enzymes such as esterase, cutinase, laccase, lignin peroxidase, manganese peroxidase, dehydrogenase, lipase, dioxygenase, and phosphoesterase were detected during the pollutant biodegradation process. Fusarium oxysporum, Fusarium solani, and Fusarium culmorum are the most studied species of this genus. Owing to their metabolic versatility, these fungal species and their enzymes represent promising tools for bioremediation applications to mitigate the adverse effects of environmental pollution.
{"title":"Fusarium as a promising fungal genus with potential application in bioremediation for pollutants mitigation: A review","authors":"Carmen Sánchez","doi":"10.1016/j.biotechadv.2024.108476","DOIUrl":"10.1016/j.biotechadv.2024.108476","url":null,"abstract":"<div><div><em>Fusarium</em> is genetically diverse and widely distributed geographically. It is one of the genera with more endophytes (which cause no damage to the host plants). This review highlights the capability of <em>Fusarium</em> species to degrade environmental pollutants and describes the biodegradation pathways of some of the emerging environmental contaminants. Some <em>Fusarium</em> species use metabolic strategies enabling them to efficiently mineralize high concentrations of toxic environmental pollutants. These fungi can degrade hydrocarbons, pesticides, herbicides, dyes, pharmaceutical compounds, explosives, plastics, and plastic additives, among other pollutants, and possess high metal biosorption capabilities. According to data from consulted reports, <em>Fusarium</em> strains showed a percentage of biodegradation of a variety of contaminants ranging between 30 % and 100 % for different tested concentrations (from 1 mg to 10 g/L) in a time range between 10 h and 90 d. Enzymes such as esterase, cutinase, laccase, lignin peroxidase, manganese peroxidase, dehydrogenase, lipase, dioxygenase, and phosphoesterase were detected during the pollutant biodegradation process. <em>Fusarium oxysporum</em>, <em>Fusarium solani</em>, and <em>Fusarium culmorum</em> are the most studied species of this genus. Owing to their metabolic versatility, these fungal species and their enzymes represent promising tools for bioremediation applications to mitigate the adverse effects of environmental pollution.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"77 ","pages":"Article 108476"},"PeriodicalIF":12.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614093","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}
Pub Date : 2024-11-07DOI: 10.1016/j.biotechadv.2024.108475
Ming-Hou Li , Han Li , Xue Zhang , Yu-Chen Liang , Cheng Li , Meng-Lin Sun , Kai Li , Chen-Guang Liu , Anthony J. Sinskey
Corynebacterium glutamicum, a well-studied industrial model microorganism, has garnered widespread attention due to its ability for producing amino acids with a long history. In recent years, research efforts have been increasingly focused on exploring its potential for producing various organic acids beyond amino acids. Organic acids, which are characterized by their acidic functional groups, have diverse applications across industries such as food, agriculture, pharmaceuticals, and biobased materials. Leveraging advancements in metabolic engineering and synthetic biology, the metabolic pathways of C. glutamicum have been broadened to facilitate the production of numerous high-value organic acids. This review summarizes the recent progress in metabolic engineering for the production of both amino acids and other organic acids by C. glutamicum. Notably, these acids include, amino acids (lysine, isoleucine, and phenylalanine), TCA cycle-derived organic acids (succinic acid, α-ketoglutaric acid), aromatic organic acids (protocatechuate, 4-amino-3-hydroxybenzoic acid, anthranilate, and para-coumaric acid), and other organic acids (itaconic acid and cis, cis-muconic acid).
{"title":"Metabolic engineering of Corynebacterium glutamicum: Unlocking its potential as a key cell factory platform for organic acid production","authors":"Ming-Hou Li , Han Li , Xue Zhang , Yu-Chen Liang , Cheng Li , Meng-Lin Sun , Kai Li , Chen-Guang Liu , Anthony J. Sinskey","doi":"10.1016/j.biotechadv.2024.108475","DOIUrl":"10.1016/j.biotechadv.2024.108475","url":null,"abstract":"<div><div><em>Corynebacterium glutamicum</em>, a well-studied industrial model microorganism, has garnered widespread attention due to its ability for producing amino acids with a long history. In recent years, research efforts have been increasingly focused on exploring its potential for producing various organic acids beyond amino acids. Organic acids, which are characterized by their acidic functional groups, have diverse applications across industries such as food, agriculture, pharmaceuticals, and biobased materials. Leveraging advancements in metabolic engineering and synthetic biology, the metabolic pathways of <em>C. glutamicum</em> have been broadened to facilitate the production of numerous high-value organic acids. This review summarizes the recent progress in metabolic engineering for the production of both amino acids and other organic acids by <em>C. glutamicum</em>. Notably, these acids include, amino acids (lysine, isoleucine, and phenylalanine), TCA cycle-derived organic acids (succinic acid, α-ketoglutaric acid), aromatic organic acids (protocatechuate, 4-amino-3-hydroxybenzoic acid, anthranilate, and para-coumaric acid), and other organic acids (itaconic acid and cis, cis-muconic acid).</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"77 ","pages":"Article 108475"},"PeriodicalIF":12.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614098","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}
Currently, global annual CO2 emissions from fossil fuel consumption are extremely high, surpassing tens of billions of tons, yet our capacity to capture and utilize CO2 remains below a small fraction of the amount generated. Microbial electrosynthesis (MES) systems, an integration of microbial metabolism with electrochemistry, have emerged as a highly efficient and promising bio-based carbon-capture-and-utilization technology over other conventional techniques. MES is a unique technology for lowering the atmospheric CO2 as well as CO2 in the biogas, and also simultaneously convert them to renewable bioenergy, such as biomethane. As such, MES techniques could be applied for biogas upgrading to generate high purity biomethane, which has the potential to meet natural gas standards. This article offers a detailed overview and assessment of the latest advancements in MES for biomethane production and biogas upgrading, in terms of selecting optimal methane production pathways and associated electron transfer processes, different electrode materials and types, inoculum sources and microbial communities, ion-exchange membrane, externally applied energy level, operating temperature and pH, mode of operation, CO2 delivery method, selection of inorganic carbon source and its concentration, start-up time, and system pressure. It also highlights the current MES challenges associated with upscaling, design and configuration, long-term stability, energy demand, techno-economics, achieving net negative carbon emission, and other operational issues. Moreover, we provide a summary of current and future opportunities to integrate MES with other unique biosystems, such as methanotrophic bioreactors, and incorporate quorum sensing, 3D printing, and machine learning to further develop MES as a better biomethane-producer and biogas upgrading technique.
目前，全球每年因消耗化石燃料而产生的二氧化碳排放量极高，已超过数百亿吨，但我们捕获和利用二氧化碳的能力却仍然只占产生量的一小部分。微生物电合成（MES）系统是微生物新陈代谢与电化学的结合，与其他传统技术相比，它是一种高效且前景广阔的生物碳捕获和利用技术。MES 是一种独特的技术，可降低大气中的二氧化碳和沼气中的二氧化碳，并同时将其转化为可再生生物能源，如生物甲烷。因此，MES 技术可用于沼气提纯，生成高纯度的生物甲烷，有望达到天然气标准。本文从选择最佳甲烷生产途径和相关电子传递过程、不同电极材料和类型、接种物来源和微生物群落、离子交换膜、外部应用能级、操作温度和 pH 值、操作模式、二氧化碳输送方法、无机碳源及其浓度的选择、启动时间和系统压力等方面，详细概述和评估了用于生物甲烷生产和沼气升级的 MES 的最新进展。本报告还强调了当前 MES 在升级、设计和配置、长期稳定性、能源需求、技术经济学、实现净负碳排放以及其他操作问题方面所面临的挑战。此外，我们还总结了当前和未来将 MES 与甲烷营养生物反应器等其他独特生物系统集成的机会，并结合了法定量传感、3D 打印和机器学习，以进一步将 MES 发展成为更好的生物甲烷生产商和沼气升级技术。
{"title":"Microbial electrosynthesis technology for CO2 mitigation, biomethane production, and ex-situ biogas upgrading","authors":"Tae Hyun Chung , Simran Kaur Dhillon , Chungheon Shin , Deepak Pant , Bipro Ranjan Dhar","doi":"10.1016/j.biotechadv.2024.108474","DOIUrl":"10.1016/j.biotechadv.2024.108474","url":null,"abstract":"<div><div>Currently, global annual CO<sub>2</sub> emissions from fossil fuel consumption are extremely high, surpassing tens of billions of tons, yet our capacity to capture and utilize CO<sub>2</sub> remains below a small fraction of the amount generated. Microbial electrosynthesis (MES) systems, an integration of microbial metabolism with electrochemistry, have emerged as a highly efficient and promising bio-based carbon-capture-and-utilization technology over other conventional techniques. MES is a unique technology for lowering the atmospheric CO<sub>2</sub> as well as CO<sub>2</sub> in the biogas, and also simultaneously convert them to renewable bioenergy, such as biomethane. As such, MES techniques could be applied for biogas upgrading to generate high purity biomethane, which has the potential to meet natural gas standards. This article offers a detailed overview and assessment of the latest advancements in MES for biomethane production and biogas upgrading, in terms of selecting optimal methane production pathways and associated electron transfer processes, different electrode materials and types, inoculum sources and microbial communities, ion-exchange membrane, externally applied energy level, operating temperature and pH, mode of operation, CO<sub>2</sub> delivery method, selection of inorganic carbon source and its concentration, start-up time, and system pressure. It also highlights the current MES challenges associated with upscaling, design and configuration, long-term stability, energy demand, techno-economics, achieving net negative carbon emission, and other operational issues. Moreover, we provide a summary of current and future opportunities to integrate MES with other unique biosystems, such as methanotrophic bioreactors, and incorporate quorum sensing, 3D printing, and machine learning to further develop MES as a better biomethane-producer and biogas upgrading technique.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"77 ","pages":"Article 108474"},"PeriodicalIF":12.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614109","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}
Pub Date : 2024-11-05DOI: 10.1016/j.biotechadv.2024.108473
Jon Del Arco , Javier Acosta , Jesús Fernández-Lucas
Deaminases, ubiquitous enzymes found in all living organisms from bacteria to humans, serve diverse and crucial functions. Notably, purine and pyrimidine deaminases, while biologically essential for regulating nucleotide pools, exhibit exceptional versatility in biotechnology. This review systematically consolidates current knowledge on deaminases, showcasing their potential uses and relevance in the field of biotechnology. Thus, their transformative impact on pharmaceutical manufacturing is highlighted as catalysts for the synthesis of nucleic acid derivatives. Additionally, the role of deaminases in food bioprocessing and production is also explored, particularly in purine content reduction and caffeine production, showcasing their versatility in this field. The review also delves into most promising biomedical applications including deaminase-based GDEPT and genome and transcriptome editing by deaminase-based systems. All in all, illustrated with practical examples, we underscore the role of purine and pyrimidine deaminases in advancing sustainable and efficient biotechnological practices. Finally, the review highlights future challenges and prospects in deaminase-based biotechnological processes, encompassing both industrial and medical perspectives.
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Pub Date : 2024-10-28DOI: 10.1016/j.biotechadv.2024.108472
Marta H.G. Costa , Inês Carrondo , Inês A. Isidro , Margarida Serra
Cell therapy manufacturing requires precise monitoring of critical parameters to ensure product quality, consistency and to facilitate the implementation of cost-effective processes. While conventional analytical methods offer limited real-time insights, integration of process analytical technology tools such as Raman spectroscopy in bioprocessing has the potential to drive efficiency and reliability during the manufacture of cell-based therapies while meeting stringent regulatory requirements. The non-destructive nature of Raman spectroscopy, combined with its ability to be integrated on-line with scalable platforms, allows for continuous data acquisition, enabling real-time correlations between process parameters and critical quality attributes.
Herein, we review the role of Raman spectroscopy in cell therapy bioprocessing and discuss how simultaneous measurement of distinct parameters and attributes, such as cell density, viability, metabolites and cell identity biomarkers can streamline on-line monitoring and facilitate adaptive process control. This, in turn, enhances productivity and mitigates process-related risks. We focus on recent advances integrating Raman spectroscopy across various manufacturing stages, from optimizing culture media feeds to monitoring bioprocess dynamics, covering downstream applications such as detection of co-isolated contaminating cells, cryopreservation, and quality control of the drug product. Finally, we discuss the potential of Raman spectroscopy to revolutionize current practices and accelerate the development of advanced therapy medicinal products.
{"title":"Harnessing Raman spectroscopy for cell therapy bioprocessing","authors":"Marta H.G. Costa , Inês Carrondo , Inês A. Isidro , Margarida Serra","doi":"10.1016/j.biotechadv.2024.108472","DOIUrl":"10.1016/j.biotechadv.2024.108472","url":null,"abstract":"<div><div>Cell therapy manufacturing requires precise monitoring of critical parameters to ensure product quality, consistency and to facilitate the implementation of cost-effective processes. While conventional analytical methods offer limited real-time insights, integration of process analytical technology tools such as Raman spectroscopy in bioprocessing has the potential to drive efficiency and reliability during the manufacture of cell-based therapies while meeting stringent regulatory requirements. The non-destructive nature of Raman spectroscopy, combined with its ability to be integrated on-line with scalable platforms, allows for continuous data acquisition, enabling real-time correlations between process parameters and critical quality attributes.</div><div>Herein, we review the role of Raman spectroscopy in cell therapy bioprocessing and discuss how simultaneous measurement of distinct parameters and attributes, such as cell density, viability, metabolites and cell identity biomarkers can streamline on-line monitoring and facilitate adaptive process control. This, in turn, enhances productivity and mitigates process-related risks. We focus on recent advances integrating Raman spectroscopy across various manufacturing stages, from optimizing culture media feeds to monitoring bioprocess dynamics, covering downstream applications such as detection of co-isolated contaminating cells, cryopreservation, and quality control of the drug product. Finally, we discuss the potential of Raman spectroscopy to revolutionize current practices and accelerate the development of advanced therapy medicinal products.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"77 ","pages":"Article 108472"},"PeriodicalIF":12.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-10-22DOI: 10.1016/j.biotechadv.2024.108467
Giulia Scapin , Ece Cagdas , Lise Marie Grav , Nathan E Lewis , Steffen Goletz , Lise Hafkenscheid
Cytokines are important regulators of immune responses, making them attractive targets for autoimmune diseases and cancer therapeutics. Yet, the significance of cytokine glycosylation remains underestimated. Many cytokines carry N- and O-glycans and some even undergo C-mannosylation. Recombinant cytokines produced in heterologous host cells may lack glycans or exhibit a different glycosylation pattern such as varying levels of galactosylation, sialylation, fucosylation or xylose addition compared to their human counterparts, potentially impacting critical immune interactions.
We focused on cytokines that are currently utilized or designed in advanced therapeutic formats, including immunocytokines, fusokines, engager cytokines, and genetically engineered ‘supercytokines.’ Despite the innovative designs of these cytokine derivatives, their glycosylation patterns have not been extensively studied. By examining the glycosylation of the human native cytokines, G-CSF and GM-CSF, interferons β and γ, TNF-α and interleukins-2, −3 -4, −6, −7, −9, −12, −13, −15, −17A, −21, and − 22, we aim to assess its potential impact on their therapeutic derivatives. Understanding the glycosylation of the native cytokines could provide critical insights into the safety, efficacy, and functionality of these next-generation cytokine therapies, affecting factors such as stability, bioactivity, antigenicity, and half-life. This knowledge can guide the choice of optimal expression hosts for production and advance the development of effective cytokine-based therapeutics and synthetic immunology drugs.
{"title":"Implications of glycosylation for the development of selected cytokines and their derivatives for medical use","authors":"Giulia Scapin , Ece Cagdas , Lise Marie Grav , Nathan E Lewis , Steffen Goletz , Lise Hafkenscheid","doi":"10.1016/j.biotechadv.2024.108467","DOIUrl":"10.1016/j.biotechadv.2024.108467","url":null,"abstract":"<div><div>Cytokines are important regulators of immune responses, making them attractive targets for autoimmune diseases and cancer therapeutics. Yet, the significance of cytokine glycosylation remains underestimated. Many cytokines carry <em>N</em>- and <em>O</em>-glycans and some even undergo <em>C</em>-mannosylation. Recombinant cytokines produced in heterologous host cells may lack glycans or exhibit a different glycosylation pattern such as varying levels of galactosylation, sialylation, fucosylation or xylose addition compared to their human counterparts, potentially impacting critical immune interactions.</div><div>We focused on cytokines that are currently utilized or designed in advanced therapeutic formats, including immunocytokines, fusokines, engager cytokines, and genetically engineered ‘supercytokines.’ Despite the innovative designs of these cytokine derivatives, their glycosylation patterns have not been extensively studied. By examining the glycosylation of the human native cytokines, G-CSF and GM-CSF, interferons β and γ, TNF-α and interleukins-2, −3 -4, −6, −7, −9, −12, −13, −15, −17A, −21, and − 22, we aim to assess its potential impact on their therapeutic derivatives. Understanding the glycosylation of the native cytokines could provide critical insights into the safety, efficacy, and functionality of these next-generation cytokine therapies, affecting factors such as stability, bioactivity, antigenicity, and half-life. This knowledge can guide the choice of optimal expression hosts for production and advance the development of effective cytokine-based therapeutics and synthetic immunology drugs.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"77 ","pages":"Article 108467"},"PeriodicalIF":12.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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