Article
Biochemical Research Methods
Yiting Shi, Tianyu Dong, Boxuan Zeng, Mingdong Yao, Ying Wang, Zexiong Xie, Wenhai Xiao, Yingjin Yuan
Summary: This study successfully manipulated the production of parthenolide, a sesquiterpene lactone and precursor for the anti-glioblastoma drug ACT001, in microorganisms through a comprehensive strategy involving P450 source screening, NADPH supply, and endoplasmic reticulum size rewiring. The highest titers of parthenolide and costunolide achieved in microbes were 31.0 mg/L and 648.5 mg/L, respectively, demonstrating the potential for sustainable production of sesquiterpene lactones and highlighting a general strategy for manipulating multiple plant-derived P450s in microbes.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Tao Yu, Quanli Liu, Xiang Wang, Xiangjian Liu, Yun Chen, Jens Nielsen
Summary: This study demonstrates the establishment of a synthetic decarboxylation cycle in the yeast cytosol, which enhances the production of reduced chemicals. By implementing rational design, metabolic rewiring, and recombinant expression, the researchers achieved a significant increase in free fatty acid yield.
Article
Biotechnology & Applied Microbiology
Zhan-Tao Zhu, Meng-Meng Du, Bei Gao, Xin-Yi Tao, Ming Zhao, Yu-Hong Ren, Feng-Qing Wang, Dong-Zhi Wei
Summary: Harnessing mitochondria for terpene biosynthesis is promising but can lead to metabolic burden and poor cell growth. Analysis shows toxicity from MVA pathway phosphorylated intermediates within mitochondria inhibits cellular functions. Combining cytoplasmic and mitochondrial engineering strategies can alleviate metabolic burden and enhance terpene production.
METABOLIC ENGINEERING
(2021)
Review
Agriculture, Multidisciplinary
Wenjuan Li, Liuwei Cui, Jie Mai, Tian-Qiong Shi, Lu Lin, Zhi-Gang Zhang, Rodrigo Ledesma-Amaro, Weiliang Dong, Xiao-Jun Ji
Summary: This review summarizes the important roles and engineering strategies of Saccharomyces cerevisiae and Yarrowia lipolytica in terpene production, discusses the future prospects and challenges, and emphasizes guidelines for future studies.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Mingkai Li, Mengyu Ma, Zhenke Wu, Xiqin Liang, Qiusheng Zheng, Defang Li, Tianyue An, Guoli Wang
Summary: Rare ginsenosides, which are deglycosylated derivatives of major ginsenosides, have better absorption and biological activity. Traditional preparation methods hindered their potential applications. Recent advances in understanding ginsenoside biosynthetic pathways and the use of synthetic biology techniques have allowed for large-scale production of rare ginsenosides. This review summarizes the identification of key enzymes involved in their biosynthesis and the construction of microbial chassis for their production, highlighting the importance of discovering more enzymes and improving their catalytic efficiencies for metabolic engineering of rare ginsenosides.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Shengli Wang, Chuanling Zhan, Shengxin Nie, Daoguang Tian, Juane Lu, Mingzhang Wen, Jianjun Qiao, Hongji Zhu, Qinggele Caiyin
Summary: In this study, a highly efficient a-farnesene-producing yeast cell factory was constructed through enzyme and metabolic engineering strategies. The most active a-farnesene synthase (AFS) from Camellia sinensis (CsAFS) was introduced into Saccharomyces cerevisiae, resulting in the highest a-farnesene production. The supply of the precursor farnesyl pyrophosphate was improved by increasing the metabolic flux of the mevalonate pathway. Site-directed mutagenesis in CsAFS and the introduction of a SKIK tag further increased a-farnesene production. The final a-farnesene titer of 28.3 g/L was obtained in a 5 L bioreactor through fed-batch fermentation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Xiao Kong, Yaokang Wu, Wenwen Yu, Yanfeng Liu, Jianghua Li, Guocheng Du, Xueqin Lv, Long Liu
Summary: In this study, efficient biosynthesis of limonene in Saccharomyces cerevisiae was achieved through metabolic engineering strategies. The metabolic flow was directed towards limonene synthesis, and the titer reached 2.63 g/L, the highest reported in S. cerevisiae.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Review
Biochemical Research Methods
Liang Sun, Yong-Su Jin
Summary: The microbial conversion of plant biomass into fuels and chemicals using engineered yeast has shown progress in efficiently converting xylose and co-utilizing it with glucose. Research investments have facilitated the simultaneous fermentation of xylose and glucose, with attention now turning towards improving xylose-utilizing efficiency and achieving robust co-fermentation under industrial conditions. Harnessing the advantageous traits of yeast xylose metabolism is expected to lead to the production of diverse fuels and chemicals.
BIOTECHNOLOGY JOURNAL
(2021)
Review
Biotechnology & Applied Microbiology
Govinda R. Navale, Mahesh S. Dharne, Sandip S. Shinde
Summary: Isoprenoids, also known as terpenoids, are diverse organic compounds found abundantly in nature, with various applications in pharmaceutical, nutraceutical, and chemical industries. Recent advancements in metabolic engineering have enabled the production of isoprenoids in heterologous host systems like Escherichia coli and Saccharomyces cerevisiae. Challenges and strategies for scale-up and engineering of isoprenoids in heterologous host systems have been discussed in detail.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Diep Thi Ngoc Nguyen, Ok Kyung Lee, Thu Thi Nguyen, Eun Yeol Lee
Summary: The review highlights recent advances in Type II methanotrophs related to multi-omics studies and metabolic engineering. It also discusses representative examples and prospects of metabolic engineering strategies for the production of suitable products.
BIOTECHNOLOGY ADVANCES
(2021)
Article
Biotechnology & Applied Microbiology
Aafke C. A. van Aalst, Sophie C. de Valk, Walter M. van Gulik, Mickel L. A. Jansen, Jack T. Pronk, Robert Mans
Summary: This paper reviews pathway engineering strategies for improving ethanol yield on glucose and/or sucrose in anaerobic cultures of Saccharomyces cerevisiae. It discusses the context dependency, theoretical impact, and potential for industrial application of different strategies.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yu Chen, Feiran Li, Jiwei Mao, Yun Chen, Jens Nielsen
Summary: Metal ions play a vital role in metabolism by affecting enzyme reactions, and a genome-scale metabolic model can predict enzyme-metal ion binding and metabolic flux changes in response to different metal ion levels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Lijuan Zhang, Xue Liu, Jiawei Li, Yonghui Meng, Guang-Rong Zhao
Summary: This study successfully constructed a Saccharomyces cerevisiae strain for betanin production, achieving high efficiency through optimizing metabolic pathways, screening and modifying enzymes, among other methods. This work is important for the development of synthetic yeast cell factories for the production of valuable betanin and other betacyanins.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Mingdong Yao, Kui Zhou, Chao Yu, Nan Liang, Wenhai Xiao, Ying Wang, Yingjin Yuan
Summary: Lycopene, a red carotenoid with antioxidant activity, is widely used in various industries. Production of lycopene in Saccharomyces cerevisiae is an economic and sustainable approach, but its yield has reached a ceiling. In this study, an integrated strategy combining ARTP mutagenesis and H2O2-induced ALE was proposed to improve the supply of upstream metabolic flux toward FPP. By enhancing the expression of CrtE and introducing an engineered CrtI mutant, the utilization of FPP towards lycopene was increased, resulting in a significant increase in lycopene production. This study highlights the effectiveness of combining metabolic engineering and adaptive evolution for natural product synthesis.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Jianxun Zhu, Tianyue An, Wenlong Zha, Ke Gao, Ting Li, Jiachen Zi
Summary: Metabolic engineering has been widely used for the production of natural medicinal molecules. However, the limited knowledge of the complex regulatory machinery of the metabolic network hindered the engineering of high-yield platforms. The N6-methyladenosine (m6A) modification of RNA plays a critical role in the regulation of gene expression. Overexpression of the yeast m6A methyltransferase IME4 remarkably altered the transcript levels of genes involved in pathways optimized for chemical production, such as glycolysis, acetyl-CoA synthesis, and shikimate/ aromatic amino acid synthesis. Furthermore, IME4 overexpression induced the key genes ACS1 and ADH2 responsible for acetyl-CoA synthesis in a transcription factor-mediated manner and significantly increased the production of isoprenoids and aromatic compounds. Manipulation of m6A adds a new layer of metabolic regulatory machinery and has the potential to be widely used in the bioproduction of various medicinal molecules.
ACTA PHARMACEUTICA SINICA B
(2023)
Review
Dentistry, Oral Surgery & Medicine
Taihiko Yamaguchi, Saki Mikami, Masana Maeda, Taishi Saito, Toshinori Nakajima, Wataru Yachida, Akihito Gotouda
Summary: This article reviews the current state of portable/wearable EMG devices for assessment of bruxism. The results show that ultra-miniaturized wearable EMG devices with performance equivalent to conventional devices have been developed and used during sleep and in the daytime, with a high level of diagnostic accuracy for sleep bruxism. However, a definite cut-off value for awake bruxism has not been established.
CRANIO-THE JOURNAL OF CRANIOMANDIBULAR & SLEEP PRACTICE
(2023)
Article
Acoustics
Christian Svane, Christian Riis Forman, Aqella Rasul, Jens Bo Nielsen, Jakob Lorentzen
Summary: This study used ultrasound and hand-held dynamometry to characterize plantar flexor muscle contractures in adults with cerebral palsy (CP). The results showed that there is a correlation between echo intensity and passive muscle stiffness as well as passive range of motion (pROM). Adults with CP had higher ultrasound echo intensity and passive muscle stiffness, and lower ankle joint pROM compared to neurologically intact adults.
ULTRASOUND IN MEDICINE AND BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Feiran Li, Yu Chen, Qi Qi, Yanyan Wang, Le Yuan, Mingtao Huang, Ibrahim E. Elsemman, Amir Feizi, Eduard J. Kerkhoven, Jens Nielsen
Summary: Researchers have constructed a proteome-constrained genome-scale protein secretory model for yeast and demonstrated its application in the production of different recombinant proteins.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Feiran Li, Le Yuan, Hongzhong Lu, Gang Li, Yu Chen, Martin K. M. Engqvist, Eduard J. Kerkhoven, Jens Nielsen
Summary: The turnover numbers (k(cat)) of enzymes are crucial for understanding cellular metabolism and physiological diversity. In this study, a deep learning approach (DLKcat) was developed to predict k(cat) values for metabolic enzymes using only substrate structures and protein sequences. The predicted k(cat) values showed good performance in a genome-scale analysis of more than 300 yeast species, and were able to explain phenotypic differences.
Article
Biochemistry & Molecular Biology
Feiran Li, Yu Chen, Mihail Anton, Jens Nielsen
Summary: Enzyme parameters are crucial for understanding, modeling, and engineering cells. Experimental measurements only cover a small portion of enzyme-compound pairs, and even less in non-model organisms. Artificial intelligence techniques have accelerated the exploration of enzyme properties by predicting them in a high-throughput manner. GotEnzymes is a comprehensive database that provides predicted enzyme parameters using AI approaches, allowing for interactive web exploration and programmatic access.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Fariba Roshanzamir, Jonathan L. Robinson, Daniel Cook, Mohammad Hossein Karimi-Jafari, Jens Nielsen
Summary: This study utilized transcriptomic data and metabolic network analyses to investigate the adaptation of metastatic tumors to the local metabolic environment. The findings suggest that metastatic tumors adopt a metabolic signature similar to their destination's primary tumors, but the extent of adaptation varies across different organs. Metastatic tumors also retain metabolic signatures associated with TNBC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Gen Zou, Jens B. Nielsen, Yongjun Wei
Summary: Recent advances in synthetic biology have revolutionized mushroom farming by shifting the focus from traditional cultivation to comprehensive applications using cutting-edge biotechnologies. Promising applications in this field include precision breeding, exploration of biosynthetic gene clusters, development of mushroom chassis cells, and construction of cell factories for high-value products.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Johan Gustafsson, Mihail Anton, Fariba Roshanzamir, Rebecka Jornsten, Eduard J. Kerkhoven, Jonathan L. Robinson, Jens Nielsen
Summary: Single-cell RNA sequencing combined with genome-scale metabolic models has the potential to unravel metabolism differences across cell types and cell states. This study develops a method for generating cell-type-specific models and evaluates the impact of RNA-Seq normalization methods on model topology. The approach successfully detects unique metabolic profiles and cancer-associated differences.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemical Research Methods
Le Yuan, Hongzhong Lu, Feiran Li, Jens Nielsen, Eduard J. Kerkhoven
Summary: In this study, a computational toolbox called HGTphyloDetect was developed, which combines high-throughput analysis with phylogenetic inference to accurately identify horizontal gene transfer (HGT) events and illustrate the transmission pathway among evolutionarily distant or closely related species. The HGTphyloDetect toolbox is user-friendly, capable of detecting HGT events with high efficiency and low false discovery rate.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Min Chen, Tingting Xie, Huan Li, Yingping Zhuang, Jianye Xia, Jens Nielsen
Summary: Supply and regulation of Gibbs free energy and precursors in cellular metabolism are essential for cellular function. In this study, we used multi-omics data under different conditions to investigate the regulation of central carbon metabolism (CCM) in yeast. We identified a metabolism-specific CCM flux regulation mechanism, which is affected by posttranslational modification and allosteric regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Analytical
Ivana Bardino Novosel, Anina Ritterband-Rosenbaum, Georgios Zampoukis, Jens Bo Nielsen, Jakob Lorentzen
Summary: This study developed and trained an image-based Convolutional Neural Network (CNN) to recognize specific movement classifiers relevant to individuals with cerebral palsy (CP). Monitoring and quantifying movement behavior in CP patients using multiple wearable sensors and CNN is of great value for improving their health outcomes.
Article
Materials Science, Multidisciplinary
Morteza Aghaee, Arun Akkala, Zulfi Alam, Rizwan Ali, Alejandro Alcaraz Ramirez, Mariusz Andrzejczuk, Andrey E. Antipov, Pavel Aseev, Mikhail Astafev, Bela Bauer, Jonathan Becker, Srini Boddapati, Frenk Boekhout, Jouri Bommer, Tom Bosma, Leo Bourdet, Samuel Boutin, Philippe Caroff, Lucas Casparis, Maja Cassidy, Sohail Chatoor, Anna Wulf Christensen, Noah Clay, William S. Cole, Fabiano Corsetti, Ajuan Cui, Paschalis Dalampiras, Anand Dokania, Gijs de Lange, Michiel de Moor, Juan Carlos Estrada Saldana, Saeed Fallahi, Zahra Heidarnia Fathabad, John Gamble, Geoff Gardner, Deshan Govender, Flavio Griggio, Ruben Grigoryan, Sergei Gronin, Jan Gukelberger, Esben Bork Hansen, Sebastian Heedt, Jesus Herranz Zamorano, Samantha Ho, Ulrik Laurens Holgaard, Henrik Ingerslev, Linda Johansson, Jeffrey Jones, Ray Kallaher, Farhad Karimi, Torsten Karzig, Cameron King, Maren Elisabeth Kloster, Christina Knapp, Dariusz Kocon, Jonne Koski, Pasi Kostamo, Peter Krogstrup, Mahesh Kumar, Tom Laeven, Thorvald Larsen, Kongyi Li, Tyler Lindemann, Julie Love, Roman Lutchyn, Morten Hannibal Madsen, Michael Manfra, Signe Markussen, Esteban Martinez, Robert McNeil, Elvedin Memisevic, Trevor Morgan, Andrew Mullally, Chetan Nayak, Jens Nielsen, William Hvidtfelt Padkaer Nielsen, Bas Nijholt, Anne Nurmohamed, Eoin OFarrell, Keita Otani, Sebastian Pauka, Karl Petersson, Luca Petit, Dmitry I. Pikulin, Frank Preiss, Marina Quintero-Perez, Mohana Rajpalke, Katrine Rasmussen, Davydas Razmadze, Outi Reentila, David Reilly, Richard Rouse, Ivan Sadovskyy, Lauri Sainiemi, Sydney Schreppler, Vadim Sidorkin, Amrita Singh, Shilpi Singh, Sarat Sinha, Patrick Sohr, Tomas Stankevic, Lieuwe Stek, Henri Suominen, Judith Suter, Vicky Svidenko, Sam Teicher, Mine Temuerhan, Nivetha Thiyagarajah, Raj Tholapi, Mason Thomas, Emily Toomey, Shivendra Upadhyay, Ivan Urban, Saulius Vaitiekenas, Kevin Van Hoogdalem, David Van Woerkom, Dmitrii V. Viazmitinov, Dominik Vogel, Steven Waddy, John Watson, Joseph Weston, Georg W. Winkler, Chung Kai Yang, Sean Yau, Daniel Yi, Emrah Yucelen, Alex Webster, Ruichen Zhao
Summary: In this study, measurements and simulations of semiconductor-superconductor heterostructure devices were conducted to observe topological superconductivity and Majorana zero modes. The devices were optimized to ensure robustness against nonuniformity and disorder. Experimental results indicate the presence of a topological superconducting phase, which is a prerequisite for experiments involving Majorana zero modes fusion and braiding.
Article
Endocrinology & Metabolism
Tao Yu, Quanli Liu, Xiang Wang, Xiangjian Liu, Yun Chen, Jens Nielsen
Summary: This study demonstrates the establishment of a synthetic decarboxylation cycle in the yeast cytosol, which enhances the production of reduced chemicals. By implementing rational design, metabolic rewiring, and recombinant expression, the researchers achieved a significant increase in free fatty acid yield.
