{"title":"Redesigning and rethinking genetic circuits: the potential of transcriptional rewiring in filamentous fungi","authors":"Alejandra Goity , Luis F Larrondo","doi":"10.1016/j.copbio.2025.103301","DOIUrl":"10.1016/j.copbio.2025.103301","url":null,"abstract":"<div><div>Fungi play vital roles in ecosystems and biotechnology, yet synthetic biology efforts have predominantly focused on the model organism <em>Saccharomyces cerevisiae</em>, with less attention given to filamentous fungi. This review explores the molecular toolkits available for gene regulatory network (GRN) manipulation in these organisms, focusing on transcriptional rewiring and promoter engineering. Beyond constitutive and inducer-responsive promoters, the use of <em>cis</em>-elements responsive to physical cues like light and temperature enables gene expression control with unprecedented spatiotemporal precision. Additionally, newly available modular toolkits further facilitate GRN rewiring for metabolic engineering and fundamental research in filamentous fungi. Using <em>Neurospora crassa</em> as a model, we illustrate how transcriptional rewiring enhances cellulase production and reveals design principles of complex circuits, such as circadian oscillators.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103301"},"PeriodicalIF":7.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747098","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}
Elizabeth R Johnson , Madeline R Joseph , Danielle Tullman-Ercek
{"title":"Engineering bacterial microcompartments to enable sustainable microbial bioproduction from C1 greenhouse gases","authors":"Elizabeth R Johnson , Madeline R Joseph , Danielle Tullman-Ercek","doi":"10.1016/j.copbio.2025.103299","DOIUrl":"10.1016/j.copbio.2025.103299","url":null,"abstract":"<div><div>One-carbon (C1) greenhouse gases are the primary driver of global climate change. Fermenting these gases into higher-value products is an attractive strategy for climate action and sustainable development. C1 gas-fermenting bacteria are promising chassis organisms, but various technical challenges hinder scale-up to industrial production levels. Bacterial microcompartments (MCPs), proteinaceous organelles that encapsulate enzymatic pathways, may confer several metabolic benefits to increase the industrial potential of these bacteria. Many species of gas-fermenting bacteria are already predicted to natively produce MCPs. Here, we describe how these organelles can be identified and engineered to encapsulate pathways that convert C1 gases into valuable chemical products.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103299"},"PeriodicalIF":7.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735270","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}
John D Hill , Hyeongmin Seo , Eleftherios T Papoutsakis
{"title":"Acetogenic mixotrophy for carbon-neutral and carbon-negative production of chemicals","authors":"John D Hill , Hyeongmin Seo , Eleftherios T Papoutsakis","doi":"10.1016/j.copbio.2025.103298","DOIUrl":"10.1016/j.copbio.2025.103298","url":null,"abstract":"<div><div>Microbial conversion of renewable carbon sources into valuable chemicals can significantly reduce our reliance on fossil resources and decrease the carbon footprint of chemical manufacturing. Of emerging interest is anaerobic, nonphotosynthetic mixotrophy (ANP mixotrophy) that simultaneously converts renewable carbohydrates and C<sub>1</sub> gases (CO<sub>2</sub> and CO) into value-added chemical products in carbon-neutral and even carbon-negative fermentations. Despite significant advances in ANP mixotrophy over the past decade, several challenges remain. We discuss key challenges for carbon-neutral/negative ANP fermentations, notably the necessity of supplying additional electrons for reduced metabolite production, the slow adoption of genetic tools, uncertainties about carbon catabolite repression, and gas transfer limitations.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103298"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725717","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}
Paul A Adamczyk , Tian Jiang , Karuna Jetty , Vijaydev Ganesan , Di Liu
{"title":"Recent developments of oleaginous yeasts toward sustainable biomanufacturing","authors":"Paul A Adamczyk , Tian Jiang , Karuna Jetty , Vijaydev Ganesan , Di Liu","doi":"10.1016/j.copbio.2025.103297","DOIUrl":"10.1016/j.copbio.2025.103297","url":null,"abstract":"<div><div>Oleaginous yeast are remarkably versatile organisms, distinguished by their natural capacities to accumulate high levels of neutral lipids and broad substrate range. With recent growing interests in engineering non-model organisms as superior biomanufacturing platforms, oleaginous yeasts have emerged as promising chassis for oleochemicals, terpenoids, organic acids, and other valuable products. Advancement in systems biology along with genetic tool development have significantly expanded our understanding of the metabolism in these species and enabled engineering efforts to produce biofuels and bioproducts from diverse feedstocks. This review examines the latest technical advances in oleaginous yeast research toward sustainable biomanufacturing. We cover recent developments in systems biology-enabled metabolism understanding, genetic tools, feedstock utilization, and strain engineering approaches for the production of various valuable chemicals.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103297"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716021","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}
Nehreen Majed , Zijian Wang , Mathew T Baldwin , Saif Mahmod Foij Uddin , Pallab Dash , April Z Gu
{"title":"Advancements in phosphorus species profiling and bioavailability assessment with implications for phosphorus sustainability","authors":"Nehreen Majed , Zijian Wang , Mathew T Baldwin , Saif Mahmod Foij Uddin , Pallab Dash , April Z Gu","doi":"10.1016/j.copbio.2025.103295","DOIUrl":"10.1016/j.copbio.2025.103295","url":null,"abstract":"<div><div>Phosphorus (P) is an essential nutrient that governs ecosystem productivity, drives global biogeochemical cycles, and plays a central role in water–energy–food nexus. The increasing scarcity of P reserves and their environmental losses necessitate precise detection to monitor P in all contexts for effective and sustainable resource management. This review highlights recent advances in analytical techniques for P speciation and bioavailability across environmental matrices, including both bulk and single-cell methods. Furthermore, recent emerging insights into microbial P cycling were discussed, particularly the role of polyphosphate and polyphosphate-accumulating organisms in dynamic P transformations. By emphasizing the sustainability implications of P, we stress the importance of precise and quantitative detection methods to inform sustainable P management and mitigate the global P crisis.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103295"},"PeriodicalIF":7.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703979","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}
Luigi Russo, Ilaria De Martino , Matteo Marchetti , Velia Siciliano
{"title":"Engineered T cells and macrophages: two arms to seize solid tumors","authors":"Luigi Russo, Ilaria De Martino , Matteo Marchetti , Velia Siciliano","doi":"10.1016/j.copbio.2025.103296","DOIUrl":"10.1016/j.copbio.2025.103296","url":null,"abstract":"<div><div>Following the breakthroughs of CAR T cells in the treatment of several hematological malignancies, clinical trials based on genetically modified immune cells are exponentially increasing. Redirecting T cell cytotoxicity against solid tumors via CARs, however, encountered several barriers that require the engineering of additional functions to improve safety, migration, efficacy, and persistence in solid tumors. Complementary strategies tried to harness macrophage properties such as cancer cell phagocytosis, cytokine release, and antigen presentation to induce broader antitumorigenic immune response. While providing a comprehensive overview on the latest technologies in the cell-based immunotherapy realm, we propose that engineering synthetic interplay between immune cells will be the next breakthrough to drive safer and more effective living therapeutics.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103296"},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703980","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}
Lars Puiman , Carolin Bokelmann , Sean D Simpson , Alfred M Spormann , Ralf Takors
{"title":"Dos and don’ts for scaling up gas fermentations","authors":"Lars Puiman , Carolin Bokelmann , Sean D Simpson , Alfred M Spormann , Ralf Takors","doi":"10.1016/j.copbio.2025.103294","DOIUrl":"10.1016/j.copbio.2025.103294","url":null,"abstract":"<div><div>Gas fermentation processes (using CO<sub>2</sub>, CO, H<sub>2</sub>, CH<sub>4</sub>) have gained significant research and commercial interest in the last years due to their potential for carbon capture and sequestration. The small economic margins of these processes necessitate the use of large-volume bioreactors. For cost-effective gas delivery, we advise using pneumatically agitated bioreactors, like bubble column reactors, compared to traditional stirred-tank reactors. Although scale-up is conventionally done on an empirical and rule-of-thumb basis, rational methods are currently available. The most important one is the knowledge-driven scaling-up approach, wherein (CFD-based) hydrodynamic and kinetic models of large-scale bioreactors guide the design of representative lab-scale experiments. We suggest several future research directions to enhance the predictive capacity of these models and thereby accelerate scaling-up gas fermentation processes.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103294"},"PeriodicalIF":7.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673556","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}
Ninfa Ramírez-Durán , Tonatiuh Moreno-Perlín , Lorna C Can-Ubando , Gauddy L Manzanares-Leal , Pablo A Moreno-Pérez , Horacio Sandoval-Trujillo , Keila Isaac-Olivé , Elisabet Aranda , Ramón Alberto Batista-García
{"title":"Advancing fungal biodegradation of nonsteroidal anti-inflammatory drugs — challenges and future perspectives","authors":"Ninfa Ramírez-Durán , Tonatiuh Moreno-Perlín , Lorna C Can-Ubando , Gauddy L Manzanares-Leal , Pablo A Moreno-Pérez , Horacio Sandoval-Trujillo , Keila Isaac-Olivé , Elisabet Aranda , Ramón Alberto Batista-García","doi":"10.1016/j.copbio.2025.103293","DOIUrl":"10.1016/j.copbio.2025.103293","url":null,"abstract":"<div><div>Environmental pollution poses serious threats to ecosystems, human health, and overall quality of life. Among the most concerning pollutants are emerging contaminants like nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used in human and veterinary medicine. These drugs and their metabolites are excreted into wastewater systems, where existing treatment methods often fail to eliminate them fully. Due to their persistence in aquatic environments, NSAIDs accumulate, necessitating innovative degradation strategies. Fungal biotransformation offers a promising solution, using the unique metabolic capabilities of unicellular yeasts and filamentous fungi. This review explores the potential of fungi to degrade NSAIDs through various enzymatic and nonenzymatic pathways. It also highlights key challenges and perspectives in the field, such as understanding NSAID–fungal cell wall interactions, the role of transcriptional factors, and the regulatory networks involved in pharmaceutical biodegradation. The goal is to advance fungal-based strategies for more effective NSAID removal from wastewater, contributing to broader environmental remediation efforts.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103293"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654708","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}
Philipp Demling , Katrin Rosenthal , Alexander Grünberger
{"title":"Window of sustainable bioprocess operation: towards merging environmental sustainability assessment and process operation at early-stage bioprocess development","authors":"Philipp Demling , Katrin Rosenthal , Alexander Grünberger","doi":"10.1016/j.copbio.2025.103292","DOIUrl":"10.1016/j.copbio.2025.103292","url":null,"abstract":"<div><div>Developing and optimizing sustainable bioprocesses require integrating technical feasibility and environmental sustainability assessment at an early stage of process development. Therefore, environmental impact estimations need to be performed alongside the development of novel bioprocesses, and ‘feasibility’ windows need to be defined, in which a bioprocess can be operated robustly and economically while being as environmentally friendly as possible. In this opinion, we summarize the progress made in the field of environmental sustainability assessment and its integration into bioprocesses at an early stage. We propose the ‘window of sustainable bioprocess operation’ (SBO window) as a concept to find operating conditions that match economic and environmental constraints. The insights obtained by the SBO window enable the back-translation of environmental constraints into bioprocess design optimizations and thus lay the foundation for a successful implementation of sustainable bioprocesses in the future.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103292"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654709","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}