Francesco Destro , Weida Wu , Prasanna Srinivasan , John Joseph , Vivekananda Bal , Caleb Neufeld , Jacqueline M. Wolfrum , Scott R. Manalis , Anthony J. Sinskey , Stacy L. Springs , Paul W. Barone , Richard D. Braatz
{"title":"The state of technological advancement to address challenges in the manufacture of rAAV gene therapies","authors":"Francesco Destro , Weida Wu , Prasanna Srinivasan , John Joseph , Vivekananda Bal , Caleb Neufeld , Jacqueline M. Wolfrum , Scott R. Manalis , Anthony J. Sinskey , Stacy L. Springs , Paul W. Barone , Richard D. Braatz","doi":"10.1016/j.biotechadv.2024.108433","DOIUrl":"10.1016/j.biotechadv.2024.108433","url":null,"abstract":"<div><p>Current processes for the production of recombinant adeno-associated virus (rAAV) are inadequate to meet the surging demand for rAAV-based gene therapies. This article reviews recent advances that hold the potential to address current limitations in rAAV manufacturing. A multidisciplinary perspective on technological progress in rAAV production is presented, underscoring the necessity to move beyond incremental refinements and adopt a holistic strategy to address existing challenges. Since several recent reviews have thoroughly covered advancements in upstream technology, this article provides only a concise overview of these developments before moving to pivotal areas of rAAV manufacturing not well covered in other reviews, including analytical technologies for rapid and high-throughput measurement of rAAV quality attributes, mathematical modeling for platform and process optimization, and downstream approaches to maximize efficiency and rAAV yield. Novel technologies that have the potential to address the current gaps in rAAV manufacturing are highlighted. Implementation challenges and future research directions are critically discussed.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"76 ","pages":"Article 108433"},"PeriodicalIF":12.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016285","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}
Guiping Gong, Bo Wu, Linpei Liu, Jianting Li, Mingxiong He
{"title":"Engineering oleaginous red yeasts as versatile chassis for the production of oleochemicals and valuable compounds: Current advances and perspectives","authors":"Guiping Gong, Bo Wu, Linpei Liu, Jianting Li, Mingxiong He","doi":"10.1016/j.biotechadv.2024.108432","DOIUrl":"10.1016/j.biotechadv.2024.108432","url":null,"abstract":"<div><p>Enabling the transition towards a future circular bioeconomy based on industrial biomanufacturing necessitates the development of efficient and versatile microbial platforms for sustainable chemical and fuel production. Recently, there has been growing interest in engineering non-model microbes as superior biomanufacturing platforms due to their broad substrate range and high resistance to stress conditions. Among these non-conventional microbes, red yeasts belonging to the genus <em>Rhodotorula</em> have emerged as promising industrial chassis for the production of specialty chemicals such as oleochemicals, organic acids, fatty acid derivatives, terpenoids, and other valuable compounds. Advancements in genetic and metabolic engineering techniques, coupled with systems biology analysis, have significantly enhanced the production capacity of red yeasts. These developments have also expanded the range of substrates and products that can be utilized or synthesized by these yeast species. This review comprehensively examines the current efforts and recent progress made in red yeast research. It encompasses the exploration of available substrates, systems analysis using multi-omics data, establishment of genome-scale models, development of efficient molecular tools, identification of genetic elements, and engineering approaches for the production of various industrially relevant bioproducts. Furthermore, strategies to improve substrate conversion and product formation both with systematic and synthetic biology approaches are discussed, along with future directions and perspectives in improving red yeasts as more versatile biotechnological chassis in contributing to a circular bioeconomy. The review aims to provide insights and directions for further research in this rapidly evolving field. Ultimately, harnessing the capabilities of red yeasts will play a crucial role in paving the way towards next-generation sustainable bioeconomy.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"76 ","pages":"Article 108432"},"PeriodicalIF":12.1,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008226","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}
Guihong Yu, Xiaoxuan Ge, Wanting Li, Linwei Ji, Song Yang
{"title":"Interspecific cross-talk: The catalyst driving microbial biosynthesis of secondary metabolites","authors":"Guihong Yu, Xiaoxuan Ge, Wanting Li, Linwei Ji, Song Yang","doi":"10.1016/j.biotechadv.2024.108420","DOIUrl":"10.1016/j.biotechadv.2024.108420","url":null,"abstract":"<div><p>Microorganisms co-exist and co-evolve in nature, forming intricate ecological communities. The interspecies cross-talk within these communities creates and sustains their great biosynthetic potential, making them an important source of natural medicines and high-value-added chemicals. However, conventional investigations into microbial metabolites are typically carried out in pure cultures, resulting in the absence of specific activating factors and consequently causing a substantial number of biosynthetic gene clusters to remain silent. This, in turn, hampers the in-depth exploration of microbial biosynthetic potential and frequently presents researchers with the challenge of rediscovering compounds. In response to this challenge, the coculture strategy has emerged to explore microbial biosynthetic capabilities and has shed light on the study of cross-talk mechanisms. These elucidated mechanisms will contribute to a better understanding of complex biosynthetic regulations and offer valuable insights to guide the mining of secondary metabolites. This review summarizes the research advances in microbial cross-talk mechanisms, with a particular focus on the mechanisms that activate the biosynthesis of secondary metabolites. Additionally, the instructive value of these mechanisms for developing strategies to activate biosynthetic pathways is discussed. Moreover, challenges and recommendations for conducting in-depth studies on the cross-talk mechanisms are presented.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"76 ","pages":"Article 108420"},"PeriodicalIF":12.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916056","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}
Song Bai , Han Luo , Hanze Tong , Yi Wu , Yingjin Yuan
{"title":"Advances on transfer and maintenance of large DNA in bacteria, fungi, and mammalian cells","authors":"Song Bai , Han Luo , Hanze Tong , Yi Wu , Yingjin Yuan","doi":"10.1016/j.biotechadv.2024.108421","DOIUrl":"10.1016/j.biotechadv.2024.108421","url":null,"abstract":"<div><p>Advances in synthetic biology allow the design and manipulation of DNA from the scale of genes to genomes, enabling the engineering of complex genetic information for application in biomanufacturing, biomedicine and other areas. The transfer and subsequent maintenance of large DNA are two core steps in large scale genome rewriting. Compared to small DNA, the high molecular weight and fragility of large DNA make its transfer and maintenance a challenging process. This review outlines the methods currently available for transferring and maintaining large DNA in bacteria, fungi, and mammalian cells. It highlights their mechanisms, capabilities and applications. The transfer methods are categorized into general methods (<em>e.g.</em>, electroporation, conjugative transfer, induced cell fusion-mediated transfer, and chemical transformation) and specialized methods (<em>e.g.</em>, natural transformation, mating-based transfer, virus-mediated transfection) based on their applicability to recipient cells. The maintenance methods are classified into genomic integration (<em>e.g.</em>, CRISPR/Cas-assisted insertion) and episomal maintenance (<em>e.g.</em>, artificial chromosomes). Additionally, this review identifies the major technological advantages and disadvantages of each method and discusses the development for large DNA transfer and maintenance technologies.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"76 ","pages":"Article 108421"},"PeriodicalIF":12.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911578","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":"Yeast surface display technology: Mechanisms, applications, and perspectives","authors":"Yibo Li , Xu Wang , Ning-Yi Zhou , Junmei Ding","doi":"10.1016/j.biotechadv.2024.108422","DOIUrl":"10.1016/j.biotechadv.2024.108422","url":null,"abstract":"<div><p>Microbial cell surface display technology, which relies on genetically fusing heterologous target proteins to the cell wall through fusion with cell wall anchor proteins, has emerged as a promising and powerful method with diverse applications in biotechnology and biomedicine. Compared to classical intracellular or extracellular expression (secretion) systems, the cell surface display strategy stands out by eliminating the necessity for enzyme purification, overcoming substrate transport limitations, and demonstrating enhanced activity, stability, and selectivity. Unlike phage or bacterial surface display, the yeast surface display (YSD) system offers distinct advantages, including its large cell size, ease of culture and genetic manipulation, the use of generally regarded as safe (GRAS) host cell, the ability to ensure correct folding of complex eukaryotic proteins, and the potential for post-translational modifications. To date, YSD systems have found widespread applications in protein engineering, waste biorefineries, bioremediation, and the production of biocatalysts and biosensors. This review focuses on detailing various strategies and mechanisms for constructing YSD systems, providing a comprehensive overview of both fundamental principles and practical applications. Finally, the review outlines future perspectives for developing novel forms of YSD systems and explores potential applications in diverse fields.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"76 ","pages":"Article 108422"},"PeriodicalIF":12.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905821","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}
Jung-Hun Kim , Minyoung Kim , Gyeongnam Park , Eunji Kim , Hocheol Song , Sungyup Jung , Young-Kwon Park , Yiu Fai Tsang , Jechan Lee , Eilhann E. Kwon
{"title":"Chemicals and fuels from lipid-containing biomass: A comprehensive exploration","authors":"Jung-Hun Kim , Minyoung Kim , Gyeongnam Park , Eunji Kim , Hocheol Song , Sungyup Jung , Young-Kwon Park , Yiu Fai Tsang , Jechan Lee , Eilhann E. Kwon","doi":"10.1016/j.biotechadv.2024.108418","DOIUrl":"10.1016/j.biotechadv.2024.108418","url":null,"abstract":"<div><p>In response to address the climate crisis, there has been a growing focus on substituting conventional refinery-derived products with those derived from biorefineries. The utilization of lipids as primary materials or intermediates for the synthesis of chemicals and fuels, which are integral to the existing chemical and petrochemical industries, is a key step in this transition. This review provides a comprehensive overview of the production of sustainable chemicals (acids and alcohols), biopolymers, and fuels (including gasoline, kerosene, biodiesel, and heavy fuel oil) from lipids derived from terrestrial and algal biomass. The production of chemicals from lipids involves diverse methods, including polymerization, epoxidation, and separation/purification. Additionally, the transformation of lipids into biofuels can be achieved through processes such as catalytic cracking, hydroprocessing, and transesterification. This review also suggests future research directions that further advance the lipid valorization processes, including enhancement of catalyst durability at harsh conditions, development of deoxygenation process with low H<sub>2</sub> consumption, investigation of precise separation of target compounds, increase in lipid accumulation in algal biomass, and development of methods that utilize residues and byproducts generated during lipid extraction and conversion.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"75 ","pages":"Article 108418"},"PeriodicalIF":12.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787240","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":"Production of pyrimidine nucleosides in microbial systems via metabolic engineering: Theoretical analysis research and prospects","authors":"Xiangjun Zhang , Pilian Niu , Huiyan Liu , Haitian Fang","doi":"10.1016/j.biotechadv.2024.108419","DOIUrl":"10.1016/j.biotechadv.2024.108419","url":null,"abstract":"<div><p>Pyrimidine nucleosides, as intermediate materials of significant commercial value, find extensive applications in the pharmaceutical industry. However, the current production of pyrimidine nucleosides largely relies on chemical synthesis, creating environmental problems that do not align with sustainable development goals. Recent progress in systemic metabolic engineering and synthetic biology has enabled the synthesis of natural products like pyrimidine nucleosides through microbial fermentation, offering a more sustainable alternative. Nevertheless, the intricate and tightly regulated biosynthetic pathways involved in the microbial production of pyrimidine nucleosides pose a formidable challenge. This study focuses on metabolic engineering and synthetic biology strategies aimed at enhancing pyrimidine nucleoside production. These strategies include gene modification, transcriptional regulation, metabolic flux analysis, cofactor balance optimization, and transporter engineering. Finally, this research highlights the challenges involved in the further development of pyrimidine nucleoside-producing strains and offers potential solutions in order to provide theoretical guidance for future research endeavors in this field.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"75 ","pages":"Article 108419"},"PeriodicalIF":12.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756992","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}
Ruizhao Jiang , Shuting Yuan , Yilong Zhou , Yuwen Wei , Fulong Li , Miaomiao Wang , Bo Chen , Huimin Yu
{"title":"Strategies to overcome the challenges of low or no expression of heterologous proteins in Escherichia coli","authors":"Ruizhao Jiang , Shuting Yuan , Yilong Zhou , Yuwen Wei , Fulong Li , Miaomiao Wang , Bo Chen , Huimin Yu","doi":"10.1016/j.biotechadv.2024.108417","DOIUrl":"10.1016/j.biotechadv.2024.108417","url":null,"abstract":"<div><p>Protein expression is a critical process in diverse biological systems. For <em>Escherichia coli</em>, a widely employed microbial host in industrial catalysis and healthcare, researchers often face significant challenges in constructing recombinant expression systems. To maximize the potential of <em>E. coli</em> expression systems, it is essential to address problems regarding the low or absent production of certain target proteins. This article presents viable solutions to the main factors posing challenges to heterologous protein expression in <em>E. coli</em>, which includes protein toxicity, the intrinsic influence of gene sequences, and mRNA structure. These strategies include specialized approaches for managing toxic protein expression, addressing issues related to mRNA structure and codon bias, advanced codon optimization methodologies that consider multiple factors, and emerging optimization techniques facilitated by big data and machine learning.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"75 ","pages":"Article 108417"},"PeriodicalIF":12.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747400","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}
Zhi-Yuan Yao , Jin-Song Gong , Jia-Yu Jiang , Chang Su , Wen-Han Zhao , Zheng-Hong Xu , Jin-Song Shi
{"title":"Unraveling the intricacies of glycosaminoglycan biosynthesis: Decoding the molecular symphony in understanding complex polysaccharide assembly","authors":"Zhi-Yuan Yao , Jin-Song Gong , Jia-Yu Jiang , Chang Su , Wen-Han Zhao , Zheng-Hong Xu , Jin-Song Shi","doi":"10.1016/j.biotechadv.2024.108416","DOIUrl":"10.1016/j.biotechadv.2024.108416","url":null,"abstract":"<div><p>Glycosaminoglycans (GAGs) are extensively utilized in clinical, cosmetic, and healthcare field, as well as in the treatment of thrombosis, osteoarthritis, rheumatism, and cancer. The biological production of GAGs is a strategy that has garnered significant attention due to its numerous advantages over traditional preparation methods. In this review, we embark on a journey to decode the intricate molecular symphony that orchestrates the biosynthesis of glycosaminoglycans. By unraveling the complex interplay of related enzymes and thorough excavation of the intricate metabolic cascades involved, GAGs chain aggregation and transportation, which efficiently and controllably modulate GAGs sulfation patterns involved in biosynthetic pathway, we endeavor to offer a thorough comprehension of how these remarkable GAGs are intricately assembled and pushes the boundaries of our understanding in GAGs biosynthesis.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"75 ","pages":"Article 108416"},"PeriodicalIF":12.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733501","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":"GLYCOCINS: The sugar peppered antimicrobials","authors":"Shimona Ahlawat , Bhupendra Nath Shukla , Vaidhvi Singh , Yogita Sharma , Pravinkumar Choudhary , Alka Rao","doi":"10.1016/j.biotechadv.2024.108415","DOIUrl":"10.1016/j.biotechadv.2024.108415","url":null,"abstract":"<div><p><u>Glyco</u>sylated bacterio<u>cins</u>, known as glycocins, were first discovered in 2011. These bioactive peptides are produced by bacteria to gain survival advantages. They exhibit diverse types of glycans and demonstrate varied antimicrobial activity. Currently, there are 13 experimentally known glycocins, with over 250 identified in silico across different bacterial phyla. Notably, glycocins are recognized for their glycan-mediated antimicrobial activity, proving effective against drug-resistant and foodborne pathogens. Many glycocins contain rare S-linked glycans. Glycosyltransferases (GTs), responsible for transferring sugar to glycocins and involved in glycocin biosynthesis, often cluster together in the producer's genome. This clustering makes them valuable for custom glycoengineering with diverse substrate specificities. Heterologous expression of glycocins has paved the way for the establishment of microbial factories for glycopeptide and glycoconjugate production across various industries. In this review, we emphasize the primary roles of fully and partially characterized glycocins and their glycosylating enzymes. Additionally, we explore how specific glycan structures facilitate these functions in antibacterial activities. Furthermore, we discuss newer approaches and increasing efforts aimed at exploiting bacterial glycobiology for the development of food preservatives and as replacements or complements to traditional antibiotics, particularly in the face of antibiotic-resistant pathogenic bacteria.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"75 ","pages":"Article 108415"},"PeriodicalIF":12.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733500","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}