Article
Biochemistry & Molecular Biology
Jorge Diaz-Rullo, Jose Eduardo Gonzalez-Pastor
Summary: In this study, we developed a novel bioinformatic strategy to predict Q-genes and found that these genes are widely enriched in cellular functions, especially in biofilm formation and virulence in bacteria, particularly in human pathogens. Experimental validation showed that altering the level of tRNA Q-modification significantly affected these physiological processes in different model bacteria, representing the first report of a general mechanism controlling biofilm formation and virulence in Gram-positive and Gram-negative bacteria. Additionally, we propose that changes in Q availability in a microbiome would impact its functionality. These findings open new avenues for the control of bacterial infections and biofilm formation by inhibiting tRNA Q-modification.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Agricultural Engineering
Zhao Yan, Jian Zhang, Jie Bao
Summary: Through 198 days of laboratory adaptive evolution, researchers successfully increased the tolerance of Zymomonas mobilis strain to phenolic aldehydes and ethanol fermentability, as well as identified a potential candidate gene for synthetic biology applications.
BIORESOURCE TECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Larissa Bessler, Navpreet Kaur, Lea-Marie Vogt, Laurin Flemmich, Carmen Siebenaller, Marie-Luise Winz, Francesca Tuorto, Ronald Micura, Ann E. Ehrenhofer-Murray, Mark Helm
Summary: This study successfully incorporated an azide-containing derivative into tRNA via transglycosylation, resulting in a semi-synthetic RNA modification called Q-L1. The incorporation of this clickable chemical entity was demonstrated in vitro and in vivo, indicating its functional integration into translation and recruitment to the ribosome. The Q-L1 modification facilitated analytics through click conjugation, and was shown to maintain tRNA substrate specificity and promote further modification in cellular systems. This study represents the first in vivo integration of a synthetic moiety into an RNA modification circuit.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Valerie de Crecy-Lagard, Marshall Jaroch
Summary: Modified nucleotides in tRNA play a critical role in bacterial physiology, although their importance in translational regulation was previously overlooked. Recent breakthroughs in identifying tRNA modification genes and improving analytical tools have shed light on the key role of tRNA modifications in bacterial regulation. Through their decoding functions in translation and their link to metabolism, tRNA modifications are emerging as important components of the bacterial regulatory toolbox.
TRENDS IN MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Xia Yi, Ling Lin, Jun Mei, Wei Wang
Summary: Transporter proteins play a crucial role in improving the tolerance of fermentation strains to lignocellulose-derived furans and phenolic inhibitors. A study identified six transporter proteins as potential candidates responsible for the tolerance of phenolic aldehydes in Zymomonas mobilis, highlighting their significant correlation with oxidoreductases and transcriptional regulators. This research provides important transporter genes as synthetic biology tools for enhancing the robustness of biorefinery strains.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2021)
Article
Biotechnology & Applied Microbiology
Xia Yi, Jianfang Wu, He Jiang, Yan Zhao, Jun Mei
Summary: The expression of certain kinase genes under phenolic aldehydes stress affects the conversion of aldehydes and the fermentability of ethanol in Zymomonas mobilis.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Xia Yi, Jun Mei, Ling Lin, Wei Wang
Summary: The study identified a dioxygenase encoding gene ZMO1721 that was differentially expressed under the stress of 4-hydroxybenzaldehyde in Z. mobilis ZM4, which was confirmed to have NADH-dependent reduction activity in phenolic aldehyde vanillin conversion. Overexpression of ZMO1721 gene improved the ethanol productivity and growth rate of Z. mobilis ZM4. These findings could serve as synthetic biology tools for modifying ethanologenic strains.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaojie Wang, Bo Wu, Xin Sui, Zhufeng Zhang, Tao Liu, Yingjun Li, Guoquan Hu, Mingxiong He, Nan Peng
Summary: CRISPR-Cas systems provide adaptive immunity to bacteria and archaea by absorbing spacers, but self-derived spacers can cause CRISPR self-interference; the species efficiently repairs CRISPR-Cas system-mediated DNA breaks using the MMEJ pathway.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Qiang Li, Remi Zallot, Brian S. MacTavish, Alvaro Montoya, Daniel J. Payan, You Hu, John A. Gerlt, Alexander Angerhofer, Valerie De Crecy-Lagard, Steven D. Bruner
Summary: This study reveals the final step of queuosine biosynthesis and demonstrates new diversity in the chemistry of iron/sulfur-dependent enzymes, providing novel insights into the mechanism of these widely conserved tRNA modifications.
Article
Biochemistry & Molecular Biology
Sergey V. Pushkarev, Valeriia A. Vinnik, Irina V. Shapovalova, Vytas K. Svedas, Dmitry K. Nilov
Summary: This study used molecular dynamics simulations to identify the amino acid residues in the active site of tRNA-guanine transglycosylase that provide efficient binding of inhibitors. It was found that the ability of inhibitors to adopt a charged state in specific environments is crucial for complex formation. The study also predicted that the introduction of substituents would have different effects on inhibiting tRNA-guanine transglycosylase and DNA repair protein poly(ADP-ribose) polymerase 1.
BIOCHEMISTRY-MOSCOW
(2022)
Article
Chemistry, Multidisciplinary
Kunlayanee Punjajom, Paul P. Sinclair, Ishika Saha, Mark Seierstad, Michael K. Ameriks, Pablo Garcia-Reynaga, Terry P. Lebold, Richmond Sarpong
Summary: A modular approach to dihydro-1,2,5-thiodiazole dioxide heterocycles is reported. Mechanistic and computational studies support an unusual 1,2 nitrogen migration mechanism for this transformation.
Article
Chemistry, Medicinal
Renne Leini, Tatu Pantsar
Summary: The KRAS SII-P is a successful tool for targeting KRAS with small molecules, as proven by the development of FDA-approved drugs and engagement with multiple mutants. A conserved water molecule in the pocket plays an important role, and its energetics and behavior were studied in the presence of inhibitors. The results highlight the significance of this water molecule in designing new inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Darren J. Hsu, Russell B. Davidson, Ada Sedova, Jens Glaser
Summary: A critical step in structure-based drug discovery is predicting the binding of a candidate molecule to a therapeutic target. Protein side chain movements hinder accurate prediction through current screening methods. We developed a high-throughput and flexible ligand pose refinement workflow called tinyIFD, which achieved successful results on diverse protein targets and demonstrated the benefit of the active learning aspect in the workflow for SARS-CoV-2 main protease inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Sean P. Henry, Maria-Elena Liosi, Joseph A. Ippolito, Kara J. Cutrona, Stefan G. Krimmer, Ana S. Newton, Joseph Schlessinger, William L. Jorgensen
Summary: The study explored the potential of modulating JAK2 kinase activity by binding to the ATP site in JH2 domain and developed compounds with nanomolar affinity and high selectivity for JAK2 JH2 domain. Crystal structure analysis revealed the binding mechanism of these compounds with JAK2 JH2, offering a new platform for seeking molecules to regulate JAK2 signaling.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Elena Shanina, Sakonwan Kuhaudomlarp, Eike Siebs, Felix F. Fuchsberger, Maxime Denis, Priscila da Silva Figueiredo Celestino Gomes, Mads H. Clausen, Peter H. Seeberger, Didier Rognan, Alexander Titz, Anne Imberty, Christoph Rademacher
Summary: Carbohydrate-protein interactions are crucial for cell-cell and host-pathogen recognition. This study identifies metal-binding pharmacophores as novel scaffolds for inhibiting Ca2+-dependent carbohydrate-protein interactions, addressing the challenge posed by the hydrophilic nature of these interactions.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Daniel J. Tao, Yuriy Slutskyy, Mikko Muuronen, Alexander Le, Philipp Kohler, Larry E. Overman
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Article
Chemistry, Medicinal
Paul Hebeisen, Bernd Kuhn, Philipp Kohler, Marcel Gubler, Walter Huber, Eric Kitas, Brigitte Schott, Joerg Benz, Catherine Joseph, Armin Ruf
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2008)
Article
Chemistry, Multidisciplinary
Philipp C. Kohler, Tina Ritschel, W. Bernd Schweizer, Gerhard Klebe, Francois Diederich
CHEMISTRY-A EUROPEAN JOURNAL
(2009)
Article
Chemistry, Multidisciplinary
Luzi Jakob Barandun, Florian Immekus, Philipp C. Kohler, Sandro Tonazzi, Bjoern Wagner, Severin Wendelspiess, Tina Ritschel, Andreas Heine, Manfred Kansy, Gerhard Klebe, Francois Diederich
CHEMISTRY-A EUROPEAN JOURNAL
(2012)
Article
Chemistry, Medicinal
Tina Ritschel, Philipp C. Kohler, Gerd Neudert, Andreas Heine, Francois Diederich, Gerhard Klebe
Article
Chemistry, Multidisciplinary
Hao Wang, Philipp Kohler, Larry E. Overman, K. N. Houk
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2012)
Article
Chemistry, Applied
Philipp Kohler, Mischa Schwaninger, Alfred Stutz, Reinhard Karge, Stefan Abele
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2018)
Article
Chemistry, Organic
Philipp Kohler, Timothe Perrin, Gabriel Schafer
Summary: DABO boronates and nitrobenzenesulfonate esters are crystalline and stable compounds, which can be used for Suzuki-Miyaura cross-coupling reactions.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Multidisciplinary
Philipp Kohler, Ivan Schindelholz, Gabriel Schafer
Summary: A new synthetic process has been developed to prepare the difficult-to-obtain 2-(3-bromophenyl)-2H-1,2,3-triazole with an overall yield of 48% and excellent purity.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Simone Tortoioti, Astrid Friedli, Alice Prud'homme, Sylvia Richard-Bildstein, Philipp Kohler, Stefan Abele, Gianvito Vile