Article
Pharmacology & Pharmacy
Yu Wang, Hongmei Tao, Wenjing Tang, Siqi Wu, Yin Tang, Ling Liu
Summary: This study aimed to investigate the alterations of myocardial succinate and fumarate levels with or without SDH inhibitor dimethyl malonate during LPS challenge. The results showed that myocardial succinate and fumarate levels were increased in the initial 9 h of LPS challenge. Dimethyl malonate increased succinate level, decreased fumarate level, aggravated cardiac dysfunction and reduced oxidative stress. After 12 h of LPS challenge, succinate level increased sharply, while fumarate level gradually decreased. Dimethyl malonate effectively reduced succinate level, increased fumarate level, improved cardiac dysfunction and inhibited interleukin-1 beta production during 12-24 h of LPS challenge.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Tianwen Zheng, Bin Xu, Yaliang Ji, Wenming Zhang, Fengxue Xin, Weiliang Dong, Ping Wei, Jiangfeng Ma, Min Jiang
Summary: The study utilized MFC technology to assist succinate production, selecting an acid-tolerant mutant JF1315 through mutagenesis and integrating the electron shuttle neutral red, significantly enhancing the glycerol utilization ability of A. succinogenes, successfully accumulating succinate with an output voltage above 300mV.
BIOTECHNOLOGY FOR BIOFUELS
(2021)
Article
Oncology
Guangxi Sun, Xingming Zhang, Jiayu Liang, Xiuyi Pan, Sha Zhu, Zhenhua Liu, Cameron M. Armstrong, Jianhui Chen, Wei Lin, Banghua Liao, Tianhai Lin, Rui Huang, Mengni Zhang, Linmao Zheng, Xiaoxue Yin, Ling Nie, Pengfei Shen, Jinge Zhao, Haoran Zhang, Jindong Dai, Yali Shen, Zhiping Li, Jiyan Liu, Junru Chen, Jiandong Liu, Zhipeng Wang, Xudong Zhu, Yuchao Ni, Dan Qin, Ling Yang, Yuntian Chen, Qiang Wei, Xiang Li, Qiao Zhou, Haojie Huang, Jin Yao, Ni Chen, Hao Zeng
Summary: This study conducted integrated genomic, epigenomic, and molecular analyses on 25 untreated primary FH-deficient RCCs, revealing low somatic mutation burden, frequent somatic copy-number alterations, and a CpG sites island methylator phenotype in these tumors. Clinical data showed that patients treated with immune checkpoint blockade-based therapy had significantly longer progression-free survival compared to those receiving antiangiogenic monotherapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Hiroko Iijima, Atsuko Watanabe, Haruna Sukigara, Kaori Iwazumi, Tomokazu Shirai, Akihiko Kondo, Takashi Osanai
Summary: Metabolically engineered cyanobacteria were able to produce valuable C4 dicarboxylic acids from CO2 by overexpressing malate dehydrogenase gene. This study demonstrates the potential of cyanobacteria as a biocatalyst for converting CO2 to carboxylic acids with industrial applications.
METABOLIC ENGINEERING
(2021)
Article
Multidisciplinary Sciences
Alexander Hooftman, Christian G. Peace, Dylan G. Ryan, Emily A. Day, Ming Yang, Anne F. McGettrick, Maureen Yin, Erica N. Montano, Lihong Huo, Juliana E. Toller-Kawahisa, Vincent Zecchini, Tristram A. J. Ryan, Alfonso Bolado-Carrancio, Alva M. Casey, Hiran A. Prag, Ana S. H. Costa, Gabriela de los Santos, Mariko Ishimori, Daniel J. Wallace, Swamy Venuturupalli, Efterpi Nikitopoulou, Norma Frizzell, Cecilia Johansson, Alexander Von Kriegsheim, Michael P. Murphy, Caroline Jefferies, Christian Frezza, Luke A. J. O'Neill
Summary: Metabolic rewiring through an inflammatory aspartate-argininosuccinate shunt induces fumarate-mediated protein succination and inflammatory effects in macrophages. Inhibition of fumarate hydratase (FH) increases fumarate levels, suppresses mitochondrial respiration, and enhances interferon responses. FH inhibition may play a pathogenic role in systemic lupus erythematosus. These findings highlight the importance of FH in regulating macrophage functions and cytokine responses.
Article
Biotechnology & Applied Microbiology
Tatsuya Kato, Ami Yokomori, Riho Suzuki, Junya Azegami, Hesham A. El Enshasy, Enoch Y. Park
Summary: The proteasome inhibitor MG-132 was found to suppress riboflavin production and SDH activity in A. gossypii, indicating a negative influence on flavoprotein homeostasis. These results elucidate the connection between riboflavin production and flavoproteins in the organism.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Claudia Durall, Kateryna Kukil, Jeffrey A. Hawkes, Alessia Albergati, Peter Lindblad, Pia Lindberg
Summary: This study successfully introduced the glyoxylate shunt into Synechocystis PCC 6803 and found that complete expression of the glyoxylate shunt can increase succinate accumulation. Supplementation with succinate dehydrogenase enzyme inhibitor and acetate can further enhance succinate accumulation in the presence of nitrate.
MICROBIAL CELL FACTORIES
(2021)
Article
Chemistry, Applied
Haoran Zhao, Minmin Li, Xiaowei Liu, Jiajie Yang, Xueyao Li, Jieyin Chen, Xiaofeng Dai, Jesus Simal-Gandara, Zhiqiang Kong, Zhizhong Li
Summary: A method for simultaneous determination of 19 SDHI fungicide residues in cereals was established using an improved QuEChERS method and UHPLC-MS/MS. The method showed good linearity and low quantification limits, and demonstrated reliability in the analysis of real samples.
Article
Microbiology
Jacqueline Gleason, Jingyu Peng, Tyre J. Proffer, Suzanne M. Slack, Cory A. Outwater, Nikki L. Rothwell, George W. Sundin
Summary: Investigations have revealed widespread resistance to fluopyram, fluxapyroxad, and boscalid in commercial tart cherry orchards in Michigan, with some orchards showing practical resistance. Genetic sequencing analysis indicates that resistant isolates did not originate from the previously prevalent boscalid-resistant strains, but evolved from fully sensitive strains in the population.
Article
Microbiology
Dennis Winkler, Sabrina Gfrerer, Johannes Gescher
Summary: The physiology of acidophilic Micrarchaeota, such as Candidatus Micrarchaeum harzensis A_DKE, remains largely unknown due to the highly expressed hypothetical proteins. In this study, isocitrate dehydrogenase (MhIDH) from A_DKE was recombinantly produced and characterized, showing specific activity for NADP(+) with low affinity likely due to a proline residue in the NADP(+) binding pocket.
Article
Cell Biology
Kira L. Tomlinson, Sebastian A. Riquelme, Swikrity Upadhyay Baskota, Marija Drikic, Ian R. Monk, Timothy P. Stinear, Ian A. Lewis, Alice S. Prince
Summary: Neutrophils play a critical role in defending against Staphylococcus aureus infection. However, S. aureus can still evade immune clearance even in the presence of a strong neutrophil response. This study reveals that S. aureus impairs neutrophil function by inducing the production of the anti-inflammatory metabolite itaconate. Itaconate inhibits neutrophil glycolysis and oxidative burst, leading to compromised bacterial killing. This evasion mechanism involves targeting neutrophil metabolism and inducing the production of itaconate.
Article
Microbiology
Stefan Spring, Manfred Rohde, Boyke Bunk, Cathrin Sproeer, Sabine Eva Will, Meina Neumann-Schaal
Summary: Strain L21-Ace-BEST, isolated from a lithifying cyanobacterial mat, belongs to a novel species and genus within the class Deferribacteres. It is an important model organism for studying anaerobic acetate degradation under hypersaline conditions. The metabolism of strain L21-Ace-BEST was characterized using biochemical studies, comparative genome analyses, and gene expression pattern evaluations. The potential use of a reversed oxidative citric acid cycle to fix CO2 was revealed through genome analysis.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Douglas Jardim-Messeder, Marcia Margis-Pinheiro, Gilberto Sachetto-Martins
Summary: The regulatory mechanisms of mitochondria in plant stress signaling are not fully understood. This study demonstrates that salicylic acid and adenine nucleotides regulate the activity of the succinate dehydrogenase complex and the production of reactive oxygen species in mitochondria. Salicylic acid induces the activity of the complex, while adenine nucleotides act through the SDH1 subunit. Adenine nucleotides regulate mitochondrial activity on the matrix side of the inner membrane, and ADP and ATP can limit mitochondrial oxygen consumption by inhibiting the cytochrome bc1 complex.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Biotechnology & Applied Microbiology
Xiuru Shen, Lingtong Liao, Guoqiang Zhang, Jingwen Zhou, Jianghua Li, Guocheng Du
Summary: In this study, lactase-producing Kluyveromyces lactis JNXR-2101 was obtained using a rapid and sensitive method based on a fluorescent substrate. The purified lactase was identified as neutral lactase with an optimum pH of 9. Knocking out a putative mannoprotein gene in K. lactis effectively promoted cell wall degradation and lactase production. After optimizing fermentation conditions, the lactase yield reached 159.62 U/mL in a 5-L fed-batch bioreactor for the mannoprotein-deficient K. lactis JNXR-2101 Delta E01057g.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Cell Biology
Wei Zhou, Gaolei Hu, Jianli He, Tianshi Wang, Yong Zuo, Ying Cao, Quan Zheng, Jun Tu, Jiao Ma, Rong Cai, Yalan Chen, Qiuju Fan, Baijun Dong, Hongsheng Tan, Qi Wang, Wei Xue, Jinke Cheng
Summary: This study demonstrates that the SENP1-Sirt3 signaling pathway controls glutaminolysis, leading to the accumulation of alpha KG during IL-4-stimulated M2 polarization of macrophages. It also reveals that SENP1-Sirt3 deacetylates GLUD1, an acetylated protein in mitochondria, and increases its activity in glutaminolysis to promote alpha KG production, ultimately leading to M2 polarization of macrophages.
Article
Biochemistry & Molecular Biology
Jennifer Bremer, Christian Richter, Harald Schwalbe, Clemens Richert
Summary: Peptidoyl RNAs are translation products of single-nucleotide without the involvement of ribosomes, containing peptide structures in their oligoribonucleotide backbones. A research team has developed a method to synthesize a stable version of peptidoyl RNA with peptide linkages within the RNA chain. UV-melting and NMR analysis showed that the folding of the peptide-linked RNA segments is not cooperative. The synthesis of double RNA-linked peptides provides a new approach for exploring their structural and biochemical properties.
Article
Biochemistry & Molecular Biology
Aikaterini C. Tsika, Angelo Gallo, Nikolaos K. Fourkiotis, Aikaterini I. Argyriou, Sridhar Sreeramulu, Frank Loehr, Vladimir V. Rogov, Christian Richter, Verena Linhard, Santosh L. Gande, Nadide Altincekic, Robin Krishnathas, Isam Elamri, Harald Schwalbe, Jan Wollenhaupt, Manfred S. Weiss, Georgios A. Spyroulias
Summary: Viral infection triggers molecular defense mechanisms, including ADP-ribosylation. Viral macro domains, which can reverse ADP-ribosylation, are potential pharmaceutical targets. GS-441524, a metabolite of remdesivir, selectively inhibits viral macro domains.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tom Landgraf, Albrecht Eduard Voelklein, Boris Fuertig, Harald Schwalbe
Summary: Riboswitches are gene regulatory elements located in untranslated mRNA regions that bind inducer molecules with high affinity and specificity. Understanding the interaction between cyclic-di-nucleotides and riboswitches provides insights into gene regulation mechanisms. Experimental and computational studies allow us to predict riboswitch gene regulation and its dependence on transcription speed, pausing, and ligand concentration.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jan Heering, Nathalie Jores, Whitney Kilu, Espen Schallmayer, Evelyn Peelen, Andreas Muehler, Hella Kohlhof, Daniel Vitt, Verena Linhard, Santosh L. Gande, Apirat Chaikuad, Sridhar Sreeramulu, Harald Schwalbe, Daniel Merk
Summary: This study elucidates the molecular basis of FXR activation by systematically studying the response of FXR ligands. Different ligands have different effects on FXR activation, which align with structural changes in the ligand binding domain of FXR. The results suggest the potential application of selective modulation of FXR dimerization and co-regulator interactions for FXR ligands.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Hannes Berg, Maria A. Wirtz Martin, Nadide Altincekic, Islam Alshamleh, Jasleen Kaur Bains, Julius Blechar, Betul Ceylan, Vanessa de Jesus, Karthikeyan Dhamotharan, Christin Fuks, Santosh L. Gande, Bruno Hargittay, Katharina F. Hohmann, Marie T. Hutchison, Sophie Marianne Korn, Robin Krishnathas, Felicitas Kutz, Verena Linhard, Tobias Matzel, Nathalie Meiser, Anna Niesteruk, Dennis J. Pyper, Linda Schulte, Sven Trucks, Kamal Azzaoui, Marcel J. J. Blommers, Yojana Gadiya, Reagon Karki, Andrea Zaliani, Philip Gribbon, Marcius da Silva Almeida, Cristiane Dinis Anobom, Anna L. Bula, Matthias Butikofer, Icaro Putinhon Caruso, Isabella Caterina Felli, Andrea T. Da Poian, Gisele Cardoso de Amorim, Nikolaos K. Fourkiotis, Angelo Gallo, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Bing Hao, Vilius Kurauskas, Lauriane Lecoq, Yunfeng Li, Nathane Cunha Mebus-Antunes, Miguel Mompean, Thais Cristtina Neves-Martins, Marti Ninot-Pedrosa, Anderson S. Pinheiro, Letizia Pontoriero, Yulia Pustovalova, Roland Riek, Angus J. Robertson, Marie Jose Abi Saad, Miguel A. Trevino, Aikaterini C. Tsika, Fabio C. L. Almeida, Ad Bax, Katherine Henzler-Wildman, Jeffrey C. Hoch, Kristaps Jaudzems, Douglas Laurents, Julien Orts, Roberta Pierattelli, Georgios A. Spyroulias, Elke Duchardt-Ferner, Jan Ferner, Boris Furtig, Martin Hengesbach, Frank Lohr, Nusrat Qureshi, Christian Richter, Krishna Saxena, Andreas Schlundt, Sridhar Sreeramulu, Anna Wacker, Julia E. Weigand, Julia Wirmer-Bartoschek, Jens Wohnert, Harald Schwalbe
Summary: This study explores novel drug design against SARS-CoV-2 through NMR screening and computational mapping. They identified multiple molecules that bind to SARS-CoV-2 proteins and studied their structural and chemical properties, providing new insights for drug development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Marie-Theres Hutchison, Giovanni Bellomo, Alexey Cherepanov, Elke Stirnal, Boris Fuertig, Christian Richter, Verena Linhard, Elina Gurewitsch, Moreno Lelli, Nina Morgner, Thomas Schrader, Harald Schwalbe
Summary: This study investigates the aggregation process of A beta 42 protein, which is directly related to the pathogenesis of Alzheimer's disease. Real-time solution NMR spectroscopy is used to track the A beta 42 aggregation kinetics and analyze the impact of low-molecular-weight inhibitors. The findings reveal the differential effects of low-molecular-weight inhibitors on early-stage aggregation.
Article
Chemistry, Multidisciplinary
Alexey Sudakov, Bozana Knezic, Martin Hengesbach, Boris Fuertig, Elke Stirnal, Harald Schwalbe
Summary: More than 170 post-transcriptional modifications of RNAs have been identified. However, the detailed investigation of these modifications is limited due to the difficulty in producing large RNAs containing these modifications. This study reports the chemo-enzymatic synthesis of RNA modifications and fluorine-modified analogs, allowing the synthesis of large RNAs. The incorporation of labeled nucleotides in the riboswitch demonstrated the applicability of the modified large RNAs in characterizing RNA fold and dynamics.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Stefan Kunert, Verena Linhard, Sara Weirich, Michel Choudalakis, Florian Osswald, Lisa Kraemer, Anja R. Koehler, Alexander Broehm, Jan Wollenhaupt, Harald Schwalbe, Albert Jeltsch
Summary: The highly expressed DNMT3A DNA methyltransferase and MECP2 methylation reader in neurons interact through their DNMT3A-ADD and MECP2-TRD domains, and the interaction between MECP2 regulates the activity and subnuclear localization of DNMT3A. The interface of these two domains was mapped, revealing that the ADD domain interacts with the TRD domain through the D529-D531 region, while the TRD domain interacts with the ADD domain through residues 214-228, including K219 and K223. The mutations at the ADD-TRD interface disrupt the cellular interaction of these proteins in NIH3T3 cells.
Editorial Material
Chemistry, Multidisciplinary
Elke Duchardt-Ferner, Jan Ferner, Boris Fuertig, Martin Hengesbach, Christian Richter, Andreas Schlundt, Sridhar Sreeramulu, Anna Wacker, Julia E. Weigand, Julia Wirmer-Bartoschek, Harald Schwalbe
Summary: The COVID-19 outbreak in December 2019 led to the establishment of international collaborations to understand and combat the virus. The NMR community has come together to study the genome and proteome of SARS-CoV-2 and test their interaction with low-molecular-weight binders. Due to the global pandemic and extended lockdowns, research has shifted from local collaborations to digital formats, allowing immediate discussion of unpublished results, data analysis, sample sharing, and coordinated research between more than 50 groups from 18 countries. Key lessons and challenges for post-pandemic research are discussed.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
J. Tassilo Grun, Jihyun Kim, Sundaresan Jayanthi, Adonis Lupulescu, Eriks Kupce, Harald Schwalbe, Lucio Frydman
Summary: Magnetization transfer experiments can provide site-specific information in nuclear magnetic resonance (NMR). Repeated saturation magnetization transfer (SMT) experiments can enhance connectivities revealed via the nuclear Overhauser effect (NOE), but may also lead to artifacts such as spill-over effects and NOE oversaturation. Another potential artifact arises when labile protons of interest are bound to 15N-labeled heteronuclei. These phenomena are experimentally demonstrated in this article, along with proposed solutions to overcome them.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Tamer Ali, Sandra Rogala, Nina M. Krause, Jasleen Kaur Bains, Maria-Theodora Melissari, Sandra Waehrisch, Harald Schwalbe, Bernhard G. Herrmann, Phillip Grote
Summary: Long non-coding RNAs can regulate cell function and other genes on the transcriptional level through mechanisms such as direct interaction with DNA and formation of RNA:dsDNA triplexes. In this study, we genetically deleted the triplex forming sequence from the lncRNA Fendrr in mice and found its partial requirement for Fendrr function in vivo. Loss of the triplex forming site in developing lungs led to dysregulation of gene programs associated with lung fibrosis, with some genes containing a triplex site directly at their promoter. We confirmed the formation of an RNA:dsDNA triplex with target promoters in vitro and implicated the synergistic role of Fendrr and the Wnt signaling pathway in lung fibrosis.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Analytical
Robert Tannenberg, Martin Paul, Bettina Roeder, Santosh L. Gande, Sridhar Sreeramulu, Krishna Saxena, Christian Richter, Harald Schwalbe, Claudia Swart, Michael G. Weller
Summary: Cardiac vascular diseases, especially acute myocardial infarction (AMI), are a major cause of death worldwide. In this study, a chemiluminescence-based immunosensor was developed for the rapid and accurate measurement of cardiac troponin I (cTnI), a specific biomarker for AMI diagnosis. The sensor achieved selective and quasi-online cTnI determination within ten minutes using a flow cell and a sensitive CMOS camera for optical readout. The sensitivity and selectivity of the sensor were tested with recombinant proteins and diluted blood plasma and serum, demonstrating its potential for clinical applications.
Article
Chemistry, Multidisciplinary
Alexey V. Cherepanov, Harald Schwalbe
Summary: The quest for atomic structures of microsecond reaction intermediates is a cutting-edge research in the field of biochemistry. However, there is currently a lack of experimental methods for preparing time-resolved samples. In this study, a single-turnover technique for nanosecond initiation and suspension of biomolecular reactions in the microsecond time domain is developed. The reactions can be started by temperature jump or direct mixing and stopped by hyperquenching in liquid cryogen at 77K. The diverse morphology of nanoscale glassy bodies, including thin sheets suitable for structure analysis by transmission electron cryomicroscopy, is observed. Furthermore, a novel method of concentrating reaction intermediates for structural studies using low-temperature techniques is presented.
Meeting Abstract
Medical Laboratory Technology
C. Swart, M. Weller, V. Delatour, M. Quaglia, M. Oztug, A. Gallo, H. Schwalbe, C. Cobbaert, A. Reid, A. Kessler, G. Nordin
CLINICA CHIMICA ACTA
(2022)
Meeting Abstract
Biophysics
Albrecht E. Voelklein, Tom Landgraf, Oliver Binas, Boris Fuertig, Christian Richter, Harald Schwalbe
BIOPHYSICAL JOURNAL
(2022)