Khadija Mu'azzam , Francisco Vitor Santos da Silva , Jason Murtagh , Maria Jose Sousa Gallagher
{"title":"A roadmap for model-based bioprocess development","authors":"Khadija Mu'azzam , Francisco Vitor Santos da Silva , Jason Murtagh , Maria Jose Sousa Gallagher","doi":"10.1016/j.biotechadv.2024.108378","DOIUrl":"10.1016/j.biotechadv.2024.108378","url":null,"abstract":"<div><p>The bioprocessing industry is undergoing a significant transformation in its approach to quality assurance, shifting from the traditional Quality by Testing (QbT) to Quality by Design (QbD). QbD, a systematic approach to quality in process development, integrates quality into process design and control, guided by regulatory frameworks. This paradigm shift enables increased operational efficiencies, reduced market time, and ensures product consistency. The implementation of QbD is framed around key elements such as defining the Quality Target Product Profile (QTPPs), identifying Critical Quality Attributes (CQAs), developing Design Spaces (DS), establishing Control Strategies (CS), and maintaining continual improvement. The present critical analysis delves into the intricacies of each element, emphasizing their role in ensuring consistent product quality and regulatory compliance.</p><p>The integration of Industry 4.0 and 5.0 technologies, including Artificial Intelligence (AI), Machine Learning (ML), Internet of Things (IoT), and Digital Twins (DTs), is significantly transforming the bioprocessing industry. These innovations enable real-time data analysis, predictive modelling, and process optimization, which are crucial elements in QbD implementation. Among these, the concept of DTs is notable for its ability to facilitate bi-directional data communication and enable real-time adjustments and therefore optimize processes. DTs, however, face implementation challenges such as system integration, data security, and hardware-software compatibility. These challenges are being addressed through advancements in AI, Virtual Reality/ Augmented Reality (VR/AR), and improved communication technologies.</p><p>Central to the functioning of DTs is the development and application of various models of differing types – mechanistic, empirical, and hybrid. These models serve as the intellectual backbone of DTs, providing a framework for interpreting and predicting the behaviour of their physical counterparts. The choice and development of these models are vital for the accuracy and efficacy of DTs, enabling them to mirror and predict the real-time dynamics of bioprocessing systems. Complementing these models, advancements in data collection technologies, such as free-floating wireless sensors and spectroscopic sensors, enhance the monitoring and control capabilities of DTs, providing a more comprehensive and nuanced understanding of the bioprocessing environment.</p><p>This review offers a critical analysis of the prevailing trends in model-based bioprocessing development within the sector.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108378"},"PeriodicalIF":16.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0734975024000727/pdfft?md5=58dea59e83c7e5f71180676414c071b2&pid=1-s2.0-S0734975024000727-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955855","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}
Qian Ma , Jinhang Yi , Yulin Tang , Zihao Geng , Chunyue Zhang , Wenchao Sun , Zhengkai Liu , Wenwen Xiong , Heyun Wu , Xixian Xie
{"title":"Co-utilization of carbon sources in microorganisms for the bioproduction of chemicals","authors":"Qian Ma , Jinhang Yi , Yulin Tang , Zihao Geng , Chunyue Zhang , Wenchao Sun , Zhengkai Liu , Wenwen Xiong , Heyun Wu , Xixian Xie","doi":"10.1016/j.biotechadv.2024.108380","DOIUrl":"10.1016/j.biotechadv.2024.108380","url":null,"abstract":"<div><p>Carbon source is crucial for the cell growth and metabolism in microorganisms, and its utilization significantly affects the synthesis efficiency of target products in microbial cell factories. Compared with a single carbon source, co-utilizing carbon sources provide an alternative approach to optimize the utilization of different carbon sources for efficient biosynthesis of many chemicals with higher titer/yield/productivity. However, the efficiency of bioproduction is significantly limited by the sequential utilization of a preferred carbon source and secondary carbon sources, attributed to carbon catabolite repression (CCR). This review aimed to introduce the mechanisms of CCR and further focus on the summary of the strategies for co-utilization of carbon sources, including alleviation of CCR, engineering of the transport and metabolism of secondary carbon sources, compulsive co-utilization in single culture, co-utilization of carbon sources via co-culture, and evolutionary approaches. The findings of representative studies with a significant improvement in the bioproduction of chemicals via the co-utilization of carbon sources were discussed in this review. It suggested that by combining rational metabolic engineering and irrational evolutionary approaches, co-utilizing carbon sources can significantly contribute to the bioproduction of chemicals.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108380"},"PeriodicalIF":16.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955880","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}
{"title":"Hydrogen production pathways in Clostridia and their improvement by metabolic engineering","authors":"Roberto Mazzoli , Simone Pescarolo , Giorgio Gilli , Gianfranco Gilardi , Francesca Valetti","doi":"10.1016/j.biotechadv.2024.108379","DOIUrl":"10.1016/j.biotechadv.2024.108379","url":null,"abstract":"<div><p>Biological production of hydrogen has a tremendous potential as an environmentally sustainable technology to generate a clean fuel. Among the different available methods to produce biohydrogen, dark fermentation features the highest productivity and can be used as a means to dispose of organic waste biomass. Within this approach, Clostridia have the highest theoretical H<sub>2</sub> production yield. Nonetheless, most strains show actual yields far lower than the theoretical maximum: improving their efficiency becomes necessary for achieving cost-effective fermentation processes. This review aims at providing a survey of the metabolic network involved in H<sub>2</sub> generation in Clostridia and strategies used to improve it through metabolic engineering. Together with current achievements, a number of future perspectives to implement these results will be illustrated.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108379"},"PeriodicalIF":16.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955840","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}
Lei Zhou , Chunmeng Tao , Xiaolin Shen, Xinxiao Sun, Jia Wang, Qipeng Yuan
{"title":"Unlocking the potential of enzyme engineering via rational computational design strategies","authors":"Lei Zhou , Chunmeng Tao , Xiaolin Shen, Xinxiao Sun, Jia Wang, Qipeng Yuan","doi":"10.1016/j.biotechadv.2024.108376","DOIUrl":"10.1016/j.biotechadv.2024.108376","url":null,"abstract":"<div><p>Enzymes play a pivotal role in various industries by enabling efficient, eco-friendly, and sustainable chemical processes. However, the low turnover rates and poor substrate selectivity of enzymes limit their large-scale applications. Rational computational enzyme design, facilitated by computational algorithms, offers a more targeted and less labor-intensive approach. There has been notable advancement in employing rational computational protein engineering strategies to overcome these issues, it has not been comprehensively reviewed so far. This article reviews recent developments in rational computational enzyme design, categorizing them into three types: structure-based, sequence-based, and data-driven machine learning computational design. Case studies are presented to demonstrate successful enhancements in catalytic activity, stability, and substrate selectivity. Lastly, the article provides a thorough analysis of these approaches, highlights existing challenges and potential solutions, and offers insights into future development directions.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108376"},"PeriodicalIF":16.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915983","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}
Changxin Fan , Ziqi Xie , Da Zheng , Ruihan Zhang , Yijin Li , Jiacheng Shi , Mingyuan Cheng , Yifei Wang , Yu Zhou , Yi Zhan , Yunjun Yan
{"title":"Overview of indigo biosynthesis by Flavin-containing Monooxygenases: History, industrialization challenges, and strategies","authors":"Changxin Fan , Ziqi Xie , Da Zheng , Ruihan Zhang , Yijin Li , Jiacheng Shi , Mingyuan Cheng , Yifei Wang , Yu Zhou , Yi Zhan , Yunjun Yan","doi":"10.1016/j.biotechadv.2024.108374","DOIUrl":"10.1016/j.biotechadv.2024.108374","url":null,"abstract":"<div><p>Indigo is a natural dye extensively used in the global textile industry. However, the conventional synthesis of indigo using toxic compounds like aniline, formaldehyde, and hydrogen cyanide has led to environmental pollution and health risks for workers. This method also faces growing economic, sustainability, and environmental challenges. To address these issues, the concept of bio-indigo or indigo biosynthesis has been proposed as an alternative to aniline-based indigo synthesis. Among various enzymes, Flavin-containing Monooxygenases (FMOs) have shown promise in achieving a high yield of bio-indigo. However, the industrialization of indigo biosynthesis still encounters several challenges. This review focuses on the historical development of indigo biosynthesis mediated by FMOs. It highlights several factors that have hindered industrialization, including the use of unsuitable chassis (<em>Escherichia coli</em>), the toxicity of indole, the high cost of the substrate L-tryptophan, the water-insolubility of the product indigo, the requirement of reducing reagents such as sodium dithionite, and the relatively low yield and high cost compared to chemical synthesis. Additionally, this paper summarizes various strategies to enhance the yield of indigo synthesized by FMOs, including redundant sequence deletion, semi-rational design, cheap precursor research, NADPH regeneration, large-scale fermentation, and enhancement of water solubility of indigo.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108374"},"PeriodicalIF":16.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903699","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}
Tian-Jie Ao , Chen-Guang Liu , Zhao-Yong Sun , Xin-Qing Zhao , Yue-Qin Tang , Feng-Wu Bai
{"title":"Anaerobic digestion integrated with microbial electrolysis cell to enhance biogas production and upgrading in situ","authors":"Tian-Jie Ao , Chen-Guang Liu , Zhao-Yong Sun , Xin-Qing Zhao , Yue-Qin Tang , Feng-Wu Bai","doi":"10.1016/j.biotechadv.2024.108372","DOIUrl":"10.1016/j.biotechadv.2024.108372","url":null,"abstract":"<div><p>Anaerobic digestion (AD) is an effective and applicable technology for treating organic wastes to recover bioenergy, but it is limited by various drawbacks, such as long start-up time for establishing a stable process, the toxicity of accumulated volatile fatty acids and ammonia nitrogen to methanogens resulting in extremely low biogas productivities, and a large amount of impurities in biogas for upgrading thereafter with high cost. Microbial electrolysis cell (MEC) is a device developed for electrosynthesis from organic wastes by electroactive microorganisms, but MEC alone is not practical for production at large scales. When AD is integrated with MEC, not only can biogas production be enhanced substantially, but also upgrading of the biogas product performed in situ. In this critical review, the state-of-the-art progress in developing AD-MEC systems is commented, and fundamentals underlying methanogenesis and bioelectrochemical reactions, technological innovations with electrode materials and configurations, designs and applications of AD-MEC systems, and strategies for their enhancement, such as driving the MEC device by electricity that is generated by burning the biogas to improve their energy efficiencies, are specifically addressed. Moreover, perspectives and challenges for the scale up of AD-MEC systems are highlighted for in-depth studies in the future to further improve their performance.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108372"},"PeriodicalIF":16.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875755","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}
{"title":"Unearthing naturally-occurring cyclic antibacterial peptides and their structural optimization strategies","authors":"Ping Zeng, Honglan Wang, Pengfei Zhang, Sharon Shui Yee Leung","doi":"10.1016/j.biotechadv.2024.108371","DOIUrl":"10.1016/j.biotechadv.2024.108371","url":null,"abstract":"<div><p>Natural products with antibacterial activity are highly desired globally to combat against multidrug-resistant (MDR) bacteria. Antibacterial peptide (ABP), especially cyclic ABP (CABP), is one of the abundant classes. Most of them were isolated from microbes, demonstrating excellent bactericidal effects. With the improved proteolytic stability, CABPs are normally considered to have better druggability than linear peptides. However, most clinically-used CABP-based antibiotics, such as colistin, also face the challenges of drug resistance soon after they reached the market, urgently requiring the development of next-generation succedaneums. We present here a detail review on the novel naturally-occurring CABPs discovered in the past decade and some of them are under clinical trials, exhibiting anticipated application potential. According to their chemical structures, they were broadly classified into five groups, including (i) lactam/lactone-based CABPs, (ii) cyclic lipopeptides, (iii) glycopeptides, (iv) cyclic sulfur-rich peptides and (v) multiple-modified CABPs. Their chemical structures, antibacterial spectrums and proposed mechanisms are discussed. Moreover, engineered analogs of these novel CABPs are also summarized to preliminarily analyze their structure-activity relationship. This review aims to provide a global perspective on research and development of novel CABPs to highlight the effectiveness of derivatives design in identifying promising antibacterial agents. Further research efforts in this area are believed to play important roles in fighting against the multidrug-resistance crisis.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108371"},"PeriodicalIF":16.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852666","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}
Yunxin Yi , Xiaofan Jin , Moutong Chen , Teodora Emilia Coldea , Haifeng Zhao
{"title":"Surfactant-mediated bio-manufacture: A unique strategy for promoting microbial biochemicals production","authors":"Yunxin Yi , Xiaofan Jin , Moutong Chen , Teodora Emilia Coldea , Haifeng Zhao","doi":"10.1016/j.biotechadv.2024.108373","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2024.108373","url":null,"abstract":"<div><p>Biochemicals are widely used in the medicine and food industries and are more efficient and safer than synthetic chemicals. The amphipathic surfactants can interact with the microorganisms and embed the extracellular metabolites, which induce microbial metabolites secretion and biosynthesis, performing an attractive prospect of promoting the biochemical production. However, the commonness and differences of surfactant-mediated bio-manufacture in various fields are largely unexplored. Accordingly, this review comprehensively summarized the properties of surfactants, different application scenarios of surfactant-meditated bio-manufacture, and the mechanism of surfactants increasing metabolites production. Various biochemical productions such as pigments, amino acids, and alcohols could be enhanced using the cloud point and the micelles of surfactants. Besides, the amphiphilicity of surfactants also promoted the utilization of fermentation substrates, especially lignocellulose and waste sludge, by microorganisms, indirectly increasing the metabolites production. The increase in target metabolites production was attributed to the surfactants changing the permeability and composition of the cell membrane, hence improving the secretion ability of microorganisms. Moreover, surfactants could regulate the energy metabolism, the redox state and metabolic flow in microorganisms, which induced target metabolites synthesis. This review aimed to broaden the application fields of surfactants and provide novel insights into the production of microbial biochemicals.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108373"},"PeriodicalIF":16.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822854","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}
{"title":"Aptamer-modified paper-based analytical devices for the detection of food hazards: Emerging applications and future perspective","authors":"Mingwei Qin , Imran Mahmood Khan , Ning Ding , Shuo Qi , Xiaoze Dong , Yin Zhang , Zhouping Wang","doi":"10.1016/j.biotechadv.2024.108368","DOIUrl":"10.1016/j.biotechadv.2024.108368","url":null,"abstract":"<div><p>Food analysis plays a critical role in assessing human health risks and monitoring food quality and safety. Currently, there is a pressing need for a reliable, portable, and quick recognition element for point-of-care testing (POCT) to better serve the demands of on-site food analysis. Aptamer-modified paper-based analytical devices (Apt-PADs) have excellent characteristics of high portability, high sensitivity, high specificity, and on-site detection, which have been widely used and concerned in the field of food safety. The article reviews the basic components and working principles of Apt-PADs, and introduces their representative applications detecting food hazards. Finally, the advantages, challenges, and future directions of Apt-PADs-based sensing performance are discussed, to provide new directions and insights for researchers to select appropriate Apt-PADs according to specific applications.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108368"},"PeriodicalIF":16.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819961","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}
David Catalán-Tatjer , Konstantina Tzimou , Lars K. Nielsen , Jesús Lavado-García
{"title":"Unravelling the essential elements for recombinant adeno-associated virus (rAAV) production in animal cell-based platforms","authors":"David Catalán-Tatjer , Konstantina Tzimou , Lars K. Nielsen , Jesús Lavado-García","doi":"10.1016/j.biotechadv.2024.108370","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2024.108370","url":null,"abstract":"<div><p>Recombinant adeno-associated viruses (rAAVs) stand at the forefront of gene therapy applications, holding immense significance for their safe and efficient gene delivery capabilities. The constantly increasing and unmet demand for rAAVs underscores the need for a more comprehensive understanding of AAV biology and its impact on rAAV production. In this literature review, we delved into AAV biology and rAAV manufacturing bioprocesses, unravelling the functions and essentiality of proteins involved in rAAV production. We discuss the interconnections between these proteins and how they affect the choice of rAAV production platform. By addressing existing inconsistencies, literature gaps and limitations, this review aims to define a minimal set of genes that are essential for rAAV production, providing the potential to advance rAAV biomanufacturing, with a focus on minimizing the genetic load within rAAV-producing cells.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"73 ","pages":"Article 108370"},"PeriodicalIF":16.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0734975024000648/pdfft?md5=72a0143a4b365ccd5efcea0c3b5c0a42&pid=1-s2.0-S0734975024000648-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818601","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}