Review
Immunology
Afreen Shadan, Avik Pathak, Ying Ma, Ranjana Pathania, Rajnish Prakash Singh
Summary: This article reviews the mechanisms, virulence factors, and other factors associated with the pathogenesis of A. baumannii infection. Additionally, it discusses the role of innate and adaptive immune response, as well as the current progress in developing innovative strategies to combat this multidrug-resistant pathogen.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Plant Sciences
Qiyao Shen, Guangzhi Dai, Vinothkannan Ravichandran, Yang Liu, Lin Zhong, Haiyan Sui, Xiangmei Ren, Nianzhi Jiao, Youming Zhang, Haibo Zhou, Xiaoying Bian
Summary: Siderophores are secreted by microorganisms to survive in iron-depleted conditions and have therapeutic potential. Eight amphiphilic siderophores, saccharochelins A-H, were identified from a rare marine-derived Saccharothrix species and showed cytotoxicity against human tumor cell lines. The fatty acid side chains of saccharochelins significantly affected cytotoxicity, indicating potential for producing more potent derivatives.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Multidisciplinary Sciences
Zhong Peng, Zizhe Hu, Zugang Li, Xiaoxue Zhang, Chaoying Jia, Tianzhi Li, Menghong Dai, Chen Tan, Zhuofei Xu, Bin Wu, Huanchun Chen, Xiangru Wang
Summary: The expanding use of antimicrobials in livestock has led to a rapid increase in antimicrobial resistance (AMR). A large-scale study on AMR in pig farms in China found that E. coli isolates from pigs and their breeding environments in all provinces showed AMR, with 91% of isolates demonstrating multidrug resistance. These isolates showed resistance to last-resort drugs and carried multiple resistance genes, virulence factor-encoding genes, and putative plasmids.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Graham A. Hudson, Annie R. Hooper, Adam J. DiCaprio, David Sarlah, Douglas A. Mitchell
Summary: The study successfully identified and synthesized a new class of natural products, named pyritides, using a combination of bioinformatics, enzymology, and synthetic methods. These pyritides have a unique structure distinct from thiopeptides, with predicted enzymatic reactions leading to the formation of a trisubstituted pyridine-based macrocycle. The research demonstrates the potential of integrating bioinformatics, enzymology, and synthesis to characterize novel natural product scaffolds with interesting structural features and biological activities.
Article
Chemistry, Multidisciplinary
Shinji Kishimoto, Ayumi Minami, Yoshimitsu Aoki, Yuya Matsubara, Shogo Watanabe, Kenji Watanabe
Summary: Pathogenic fungi of Aspergillus section Fumigati are capable of producing various secondary metabolites. This study reports the isolation of fumimycin and a new compound named lentofuranine from A. lentulus. These compounds were found to be assembled through a nonenzymatic condensation involving a polyketide intermediate from the terrein biosynthetic pathway and a highly reactive azlactone intermediate. The formation of an unusual carbon skeleton is attributed to the reactivity of azlactone.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Simon Ernst, Alexander N. Volkov, Melina Stark, Lea Hoelscher, Katharina Steinert, Susanne Fetzner, Ulrich Hennecke, Steffen Lorenz Drees
Summary: Quorum sensing regulates the synthesis of azetidine-derived natural products in the opportunistic pathogen Pseudomonas aeruginosa. In this study, the researchers engineered P. aeruginosa to express the biosynthetic azegene cluster, leading to the discovery of two new products. Further investigation revealed the importance of these products in biological activity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yalong Zhang, Jian Bai, Le Zhang, Chen Zhang, Bingyu Liu, Youcai Hu
Summary: A unique self-resistance mechanism for fungal antibiotics was discovered, utilizing an oxidative-reductive cycle to prevent self-harm. This work contributes to the understanding of antibiotic biosynthesis and resistance mechanisms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Cedric Couturier, Sebastian Gross, Alexander von Tesmar, Judith Hoffmann, Selina Deckarm, Anouchka Fievet, Nelly Dubarry, Thomas Taillier, Christoph Poeverlein, Heike Stump, Michael Kurz, Luigi Toti, Sabine Haag Richter, Dietmar Schummer, Philippe Sizun, Michael Hoffmann, Ram Prasad Awal, Nestor Zaburannyi, Kirsten Harmrolfs, Joachim Wink, Emilie Lessoud, Thierry Vermat, Veronique Cazals, Sandra Silve, Armin Bauer, Michael Mourez, Laurent Fraisse, Corinne Leroi-Geissler, Astrid Rey, Stephanie Versluys, Eric Bacque, Rolf Mueller, Stephane Renard
Summary: This article describes the myxobacterial natural product Corramycin isolated from Corallococcus coralloides. Corramycin exhibits anti-Gram-negative activity against Escherichia coli and is taken up via two transporter systems. The biosynthetic gene cluster (BGC) of Corramycin was identified and a biosynthesis model was proposed. The absolute configuration of the molecule was elucidated through bioinformatic analysis and total synthesis. Animal experiments confirmed the antibacterial effect of Corramycin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Multidisciplinary Sciences
Juan Chen, Huyue Zhou, Jingbin Huang, Rong Zhang, Xiancai Rao
Summary: This review explores the impact of sub-MICs of antibiotics on the virulence of Staphylococcus aureus, focusing on various aspects such as changes in cell morphology, virulence factor expression, bacterial adherence and invasion, biofilm formation, and small-colony variant production. Antibiotics at sub-MIC levels can alter bacterial virulence in S. aureus, leading to deformed cells, abnormal immune responses, and changes in disease development. The study also addresses the mechanisms underlying these antibiotic-induced alterations in virulence.
JOURNAL OF ADVANCED RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Andrew J. J. Devine, Alice E. E. Parnell, Catherine R. R. Back, Nicholas R. R. Lees, Samuel T. T. Johns, Ainul Z. Z. Zulkepli, Rob Barringer, Katja Zorn, James E. M. Stach, Matthew P. P. Crump, Martin A. A. Hayes, Marc W. W. van der Kamp, Paul R. R. Race, Christine L. L. Willis
Summary: This study reveals the key epoxidation reaction in the synthesis of Abyssomicin C and the structure of the enzyme AbyV involved in this reaction. The combination of selective carbon-13 labeling with NMR spectroscopy proves to be an important tool in studying enzyme-catalyzed reactions in vitro.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Anton P. Tyurin, Vera A. Alferova, Alexander S. Paramonov, Maxim V. Shuvalov, Gulnara K. Kudryakova, Eugene A. Rogozhin, Alexander Y. Zherebker, Vladimir A. Brylev, Alexey A. Chistov, Anna A. Baranova, Mikhail V. Biryukov, Igor A. Ivanov, Igor A. Prokhorenko, Natalia E. Grammatikova, Tatyana V. Kravchenko, Elena B. Isakova, Elena P. Mirchink, Elena G. Gladkikh, Elena V. Svirshchevskaya, Andrey V. Mardanov, Aleksey V. Beletsky, Milita V. Kocharovskaya, Valeriya V. Kulyaeva, Alexander S. Shashkov, Dmitry E. Tsvetkov, Nikolay E. Nifantiev, Alexander S. Apt, Konstantin B. Majorov, Svetlana S. Efimova, Nikolai V. Ravin, Evgeny N. Nikolaev, Olga S. Ostroumova, Genrikh S. Katrukha, Olda A. Lapchinskaya, Olga A. Dontsova, Stanislav S. Terekhov, Ilya A. Osterman, Zakhar O. Shenkarev, Vladimir A. Korshun
Summary: A novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812, including gausemycins A and B, have been reported. These compounds exhibit pronounced activity against Gram-positive bacteria and show significant differences in mechanism compared to known glyco- and lipopeptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Engineering, Multidisciplinary
Nur Nabilah Mohd Noor, Nur Hazirah Kamaruzaman, Adel Al-Gheethi, Radin Maya Saphira Radin Mohamed, Md. Sohrab Hossain
Summary: The environmental pollution caused by antibiotics has had a serious impact on human health and the ecosystem. However, there is a lack of critical reviews and recent technologies for the removal of antibiotics in wastewater. This study provides a summary of the strategies for removing various antibiotics using photocatalysis of bio-nanoparticles, highlighting their novelty. The review compares different methods and discusses the factors affecting the photocatalysis process.
AIN SHAMS ENGINEERING JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Huayue Li, Xiao Han, Yujing Dong, Shanshan Xu, Chao Chen, Yingang Feng, Qiu Cui, Wenli Li
Summary: Bacillaenes, a class of poly-unsaturated enamines produced by Bacillus strains, are found to play dual roles as antibiotics and biofilm enhancers. This study reveals the instability of bacillaenes and their potential for stabilizing the scaffold through chemical modification. The findings suggest their importance in self-protection of Bacillus through accelerated biofilm formation in a dose-dependent manner.
Article
Multidisciplinary Sciences
Jacob Tickner, Sophia Hawas, Makrina Totsika, Johanna J. Kenyon
Summary: Identification of novel therapeutic targets is crucial for combating infections caused by extensively drug-resistant Acinetobacter baumannii. This study demonstrates that the outer membrane protein Wzi plays a key role in the assembly of the capsular polysaccharide layer on the bacterial cell surface. Loss of Wzi results in reduced cell-associated CPS and increased shedding of CPS material in the extracellular environment. Additionally, genetic analysis reveals the presence of diverse nucleotide sequences in the wzi gene across the species, suggesting a potential link between wzi type and CPS structure.
SCIENTIFIC REPORTS
(2021)
Article
Plant Sciences
Hiyoung Kim, Jun-Yong Kim, Chang-hun Ji, Dongho Lee, Sang Hee Shim, Hwang-Soo Joo, Hahk-Soo Kang
Summary: The genome of S. indonesiensis contains many silent BGCs, but when cultured in acidic pH, it produces new metabolites not observed at neutral pH. The extract from the acidic culture displayed antivirulence activity against MRSA. New glycosylated aromatic polyketides, acidonemycins A-C, and their responsible BGC were identified.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Organic
Melanie Trobe, Till Schreiner, Martin Vareka, Sebastian Grimm, Bernhard Woelfl, Rolf Breinbauer
Summary: This study presents a method for synthesizing teraryl-based alpha-helix mimetics and enhancing their water solubility using pyridine-containing boronic acid building blocks. The researchers have successfully synthesized pyridine-based boronic acid building blocks decorated with amino acid side chains relevant to protein-protein interactions. The study also reveals the influence of pyridine rings on the solubility of teraryls.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Melanie Trobe, Julia Blesl, Martin Vareka, Till Schreiner, Rolf Breinbauer
Summary: Teraryl-based alpha-helix mimetics have been synthesized using a modular and flexible approach, where a benzene core unit with two halide leaving groups of differentiated reactivity was used. The issue of hydrolysis during cross-coupling was resolved by using para-bromo iodoarene core fragments. A complete set of para-bromoiodoarene core fragments decorated with side chains of all relevant amino acids for PPI was reported. Some of the nucleophilic side chains were provided in a protected form to be compatible with general cross-coupling conditions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Melanie Trobe, Martin Vareka, Till Schreiner, Patrick Dobrounig, Carina Doler, Ella B. Holzinger, Andreas Steinegger, Rolf Breinbauer
Summary: Teraryl-based alpha-helix mimetics have been synthesized using a modular and flexible approach in order to inhibit protein-protein interactions (PPI). The synthesis method involves the use of a benzene core unit with two leaving groups of differentiated reactivity in Pd-catalyzed cross-coupling for teraryl assembly. Core fragments corresponding to previously missing amino acids have been reported, completing the set of relevant amino acid analogues.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Florian J. Gisdon, Christian G. Feiler, Oxana Kempf, Johannes M. Foerster, Jonathan Haiss, Wulf Blankenfeldt, G. Matthias Ullmann, Elisa Bombarda
Summary: In this study, the catalytic mechanism of the PCS-like enzyme from the cyanobacterium Nostoc sp. (NsPCS) was investigated. By combining structural, spectroscopic, thermodynamic, and theoretical techniques, several crystal structures of NsPCS were obtained, capturing different states of the catalyzed chemical reaction. NsPCS was found to be a relatively slow enzyme, whose activity is sensitive to the redox state of the substrate. The study also suggests that NsPCS may function as part of a redox sensing system.
ACS CHEMICAL BIOLOGY
(2022)
Article
Genetics & Heredity
Danielle Heller, Isabel Amaya, Aleem Mohamed, Ilzat Ali, Dmitri Mavrodi, Padraig Deighan, Viknesh Sivanathan
Summary: This study constructed an overexpression library and screened the genes of a bacteriophage, finding that these gene products can inhibit the growth of mycobacteria, providing important insights into phage-host interactions and potential strategies for bacterial manipulation.
G3-GENES GENOMES GENETICS
(2022)
Review
Chemistry, Multidisciplinary
Leo Krammer, Rolf Breinbauer
Summary: Activity-based protein profiling (ABPP) is a useful proteomic tool that measures the activity of enzymes or proteins in their cellular environment. It can annotate the function of uncharacterized proteins and investigate the target profile of small molecule inhibitors. However, ABPP of oxidoreductases has received less attention compared to other enzyme classes.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mostafa M. Hamed, Ahmed S. Abdelsamie, Katharina Rox, Christian Schuetz, Andreas M. Kany, Teresa Roehrig, Stefan Schmelz, Wulf Blankenfeldt, Alejandro Arce-Rodriguez, Jose Manuel Borrero-de Acuna, Dieter Jahn, Jessica Rademacher, Felix C. Ringshausen, Nina Cramer, Burkhard Tuemmler, Anna K. H. Hirsch, Rolf W. Hartmann, Martin Empting
Summary: Pseudomonas aeruginosa is a dangerous opportunistic pathogen with alarming resistances to antibiotics. Disarming the bacteria by interfering with their quorum sensing system shows promise as an alternative strategy. This study reports the design and optimization of PqRs inverse agonists, which effectively suppress bacterial pathogenicity and show activity against clinical isolates.
Article
Biotechnology & Applied Microbiology
Tuo Li, Annika J. E. Borg, Leo Krammer, Rolf Breinbauer, Bernd Nidetzky
Summary: This study demonstrates a biocatalytic process for the reaction-intensified production of di-C-beta-glucosides from sucrose, which are rare natural plant products with unique properties. The synthesis proceeds through an iterative two-fold C-glycosylation reaction catalyzed by a kumquat di-C-glycosyltransferase and uses UDP-Glc provided by a soybean sucrose synthase. The di-C-glycosylation is driven to completion with a constant supply of UDP-Glc, resulting in high yields of di-C-glucosides.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Julia Kriegesmann, Thomas Schlatzer, Kateryna Che, Claudia Altdorf, Susanne Huhmann, Hanspeter Kaehlig, Dennis Kurzbach, Rolf Breinbauer, Christian F. W. Becker
Summary: We demonstrated the extension of chemoselective Pd-catalyzed cysteine allylation reaction to stapling and the subsequent modification of alkene-containing staples to introduce additional probes into stabilized peptides. The introduction of fluorophore and PEG moieties into stapled peptides was achieved using bioorthogonal thiol-ene and Diels-Alder reactions. The structural implications of allyl staples, when used to replace conformationally relevant disulfide bridges, were investigated in a selective integrin alpha(3)beta(1) binder (LXY3) to enhance stability and binding affinity.
Article
Chemistry, Multidisciplinary
Jan Wichmann, Janine Mayer, Mattes Hintmann, Peer Lukat, Wulf Blankenfeldt, Rebekka Biedendieck
Summary: In this study, we successfully enhanced the crystallizability of a penicillin G acylase (PGA) from Bacillus sp. FJAT-27231 (FJAT-PGA) using protein engineering techniques. The improvements were achieved through surface entropy reduction and strengthening of hydrophobic interactions at crystal contacts, leading to accelerated crystallization, lower required PGA and precipitant concentrations, increased crystal yield, and improved impurity tolerance. A total of twelve amino acid exchanges and one deletion resulted in the best crystallizability achieved in this study.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Cell Biology
Lisa Poltl, Maksym Kitsera, Sandra Raffl, Stefan Schild, Amar Cosic, Sabine Kienesberger, Katrin Unterhauser, Georg Raber, Christian Lembacher-Fadum, Rolf Breinbauer, Gregor Gorkiewicz, Carlos Sebastian, Gerald Hoefler, Ellen L. Zechner
Summary: The DNA-alkylating metabolite tilimycin is a microbial genotoxin that causes colitis in individuals carrying til+ Klebsiella spp. Intestinal stem cells are affected by tilimycin-induced DNA damage, leading to genetic aberrations and increased disease susceptibility in the colon. The presence of tilimycin-producing Klebsiella results in higher frequencies and more mutations per individual compared to non-producing mutants.
Article
Chemistry, Multidisciplinary
Tatiana E. Gorelik, Peer Lukat, Christian Kleeberg, Wulf Blankenfeldt, Rolf Mueller
Summary: This study evaluated the performance of molecular replacement (MR) procedures for structure analysis of small-molecule crystal structures from 3D electron diffraction (ED) data. By using different data types and search models, MR was successfully conducted at a resolution of 2 angstrom for the crystal structure of Bi-3812.
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2023)
Article
Multidisciplinary Sciences
Fangfang Chen, Israfil Yalcin, Mingming Zhao, Chutao Chen, Wulf Blankenfeldt, Frank Pessler, Konrad Buessow
Summary: cis-Aconitate decarboxylase (ACOD1, IRG1) converts cis-aconitate to itaconate, an immunomodulatory and antibacterial metabolite. Mouse ACOD1 is about five times more active than human ACOD1, despite both enzymes having identical active site residues. By introducing isoleucine at position 154 in human ACOD1, which is naturally methionine, the activity of human ACOD1 increased. The change in ACOD1 sequence at position 154 during human evolution leads to a significant decrease in activity, possibly providing a selective advantage in diseases like cancer.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Elien Grajchen, Melanie Loix, Paulien Baeten, Beatriz F. Corte-Real, Ibrahim Hamad, Sam Vanherle, Mansour Haidar, Jonas Dehairs, Jelle Y. Broos, James M. Ntambi, Robert Zimmermann, Rolf Breinbauer, Piet Stinissen, Niels Hellings, Sanne G. S. Verberk, Gijs Kooij, Martin Giera, Johannes V. Swinnen, Bieke Broux, Markus Kleinewietfeld, Jerome J. A. Hendriks, Jeroen F. J. Bogie
Summary: The imbalance between pathogenic and protective T cell subsets is a key feature of autoimmune disorders such as multiple sclerosis (MS). The molecular mechanisms underlying the impact of fatty acid metabolism on T cell physiology and autoimmunity are poorly understood. The study reveals that fatty acid desaturation by SCD1 acts as an endogenous brake on regulatory T-cell differentiation and enhances autoimmunity, suggesting potential therapeutic strategies for autoimmune disorders such as MS.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Chemistry, Applied
Maria Degli Innocenti, Till Schreiner, Rolf Breinbauer
ADVANCED SYNTHESIS & CATALYSIS
(2023)
