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)
Article
Chemistry, Organic
Michael Kohr, Christine Walt, Jan Dastbaz, Rolf Mueller, Uli Kazmaier
Summary: Myxoprincomide, a secondary metabolite of Myxococcus xanthus DK 1622, was successfully synthesized for the first time. The synthetic natural product was obtained as an isomeric mixture, which was also found in the isolated natural product.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kathryn Trentadue, Chia-Fu Chang, Ansel Nalin, Richard E. Taylor
Summary: The ambruticins, a family of anti-fungal natural products, are characterized by a divinylcyclopropane core adorned with a pair of pyran rings. The biosynthesis of these compounds involves a polyketide synthase pathway, with a diol intermediate known as ambruticin J. Researchers have reported the first enantioselective total synthesis of ambruticin J using a triply convergent synthetic route.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Yeonghun Song, Jae Hyun Kim, Young Chan Kim, Sanghee Kim
Summary: Efforts towards the first total synthesis of (-)-oxazolomycin B and (+)-oxazolomycin C from the intermediate of our previous synthesis of (+)-neoxazolomycin are reported. The syntheses were achieved in a longest linear sequence of 25 steps from the amino acid serine in 3.6 and 2.7 % overall yields, respectively. The efficiency of our approach is derived from silyl triflate-mediated reductive oxazolidine ring-opening and Furstner's Ru-catalyzed hydrosilylation and protodesilylation reactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Plant Sciences
Chantal D. Bader, Patrick A. Haack, Fabian Panter, Daniel Krug, Rolf Mueller
Summary: Recent advances in genome sequencing have revealed a significant gap between the potential capacity of microorganisms to produce secondary metabolites and the number actually detected. By utilizing two different mass spectrometry platforms, this study identified complementary methods for detecting known and unknown metabolites in myxobacterial strains, ultimately increasing the chances of discovering new secondary metabolites. Additionally, analyzing both liquid and plate cultures of the strains led to the detection of a higher number of molecular features, highlighting the importance of diverse cultivation conditions in metabolomics studies.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Organic
Tomohiro Tsutsumi, Moe Matsumoto, Hitomi Iwasaki, Kei Tomisawa, Keita Komine, Hayato Fukuda, Jacques Eustache, Rolf Jansen, Susumi Hatakeyama, Jun Ishihara
Summary: This study describes the first total synthesis of thuggacin cmc-A and the confirmation of its absolute structure. The thuggacin family of antibiotics is of interest due to its antibiotic activity against Mycobacterium tuberculosis. Through a stereocontrolled approach, all seven stereogenic centers in thuggacin cmc-A were constructed to match the stereochemistry of thuggacin-A, confirming the stereostructure of the compound.
Article
Chemistry, Multidisciplinary
Juan Xiong, Peng-Jun Zhou, Hao-Wen Jiang, Ting Huang, Yu-Hang He, Ze-Yu Zhao, Yi Zang, Yeun-Mun Choo, Xiaojuan Wang, Amar G. Chittiboyina, Pankaj Pandey, Mark T. Hamann, Jia Li, Jin-Feng Hu
Summary: Forrestiacids A and B are novel [4+2] pentaterpenoids derived from Pseudotsuga forrestii, exhibiting potent inhibitory activities against ATP-citrate lyase and potential for treating glycolipid metabolic disorders. Compound 1 also effectively attenuated de novo lipogenesis, providing a new chemical class for developing therapeutic agents for ACL-related diseases.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Min Woo Ha, Jonghoon Kim, Seung-Mann Paek
Summary: The discovery of novel marine natural products often leads to efforts in finding new therapeutic ingredients. Due to the complexity and uniqueness of substances produced in the marine environment, there have been cases where the structures were incorrectly assigned despite the use of modern chemical techniques. Organic chemical synthesis and thorough spectroscopic data inspection are crucial in refuting inaccuracies in proposed structures.
Review
Engineering, Environmental
Adeyemi S. Adeleye, Jie Xue, Yixin Zhao, Alicia A. Taylor, Jenny E. Zenobio, Yian Sun, Ziwei Han, Omobayo A. Salawu, Yurong Zhu
Summary: Pharmaceuticals and personal care products (PPCPs) are commonly found in wastewater and the environment, primarily entering municipal wastewater systems through human excretion and also from hospitals, PPCPs manufacturers, and agriculture. The most abundant PPCPs in raw wastewater include analgesics, antibiotics, and stimulants. In conventional wastewater treatment plants, most removal of PPCPs occurs during secondary treatment, with an overall removal rate exceeding 90%.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Jiawei Sun, He Yang, Wenjun Tang
Summary: This tutorial review summarizes the total synthesis of complex dimeric natural products and discusses various dimerization strategies. By highlighting selected representative examples, it aims to demonstrate the recent tactics of dimerization and provide insights on structural and chemical properties of related natural products, promoting advancements in organic synthesis and biological studies.
CHEMICAL SOCIETY REVIEWS
(2021)
Review
Chemistry, Medicinal
Guoqing Fang, Hongjuan Chen, Zhiyun Cheng, Zilong Tang, Yichao Wan
Summary: Heterocycles, especially azaindole derivatives, have become important sources of kinase inhibitors for drug design, due to their ability to form hydrogen bonds in ATP-binding sites. This review focuses on the recent development of azaindole derivatives as potential kinase inhibitors, targeting various kinases such as AAK1, ALK, AXL, Cdc7, CDKs, DYRK1A, FGFR4, PI3K, and PIM kinases. The structure-activity relationships and binding modes of these derivatives are also elucidated. This review provides insights for medicinal chemists in the rational design of more potent kinase inhibitors with the azaindole scaffold.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Debobrata Paul, Ashis Kundu, Sanu Saha, Rajib Kumar Goswami
Summary: This feature article highlights total synthesis as a reliable tool for confirming the structure of natural products. Despite advances in spectroscopic techniques, structural misassignments of natural products remain common. Recent case studies have shown that chemical synthesis can be used to revise the structures of natural products.
CHEMICAL COMMUNICATIONS
(2021)
Review
Medicine, Research & Experimental
M. Vijaykrishnaraj, Kuiwu Wang
Summary: Natural products found in various natural foods have potential biological activities, including plants, fruits, vegetables, and marine life. The biochemical reaction known as advanced glycation end products (AGEs) in the human body contributes to the pathogenesis of diabetic complications. Researchers are exploring the use of food-derived natural products to control AGEs-related disease complications.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Bing-Chao Yan, Min Zhou, Jian Li, Xiao-Nian Li, Shi-Jun He, Jian-Ping Zuo, Han-Dong Sun, Ang Li, Pema-Tenzin Puno
Summary: Isoscopariusin A, isolated from Isodon scoparius, was identified as an unsymmetrical meroditerpenoid with a sterically congested carbon skeleton. Gram-scale synthesis was achieved in 12 steps, with selective inhibition of T-cell proliferation as a significant biological activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Bo Yin, Xiaohuan Li, Zi-Xiang Li, Xiao-Xin Zhu, Lan Zhang, Xian-Li Zhou, Jin-Bu Xu, Feng-Zheng Chen, Pei Tang, Feng Gao
Summary: (-)-Adenophorone, a compound with a unique tricyclo[4.3.1.0(5,9)]decane skeleton, was isolated from Eupatorium adenopharum Spreng. Its structure was determined using spectroscopic analysis, X-ray crystallography, and bioinspired total synthesis. The synthesis of its precursor, (+)-euptox A, was achieved in 8 steps from commercially available (-)-carvone, demonstrating excellent diastereoselectivity. Bioinspired synthesis of (-)-adenophorone was achieved from a plausible biogenetic precursor via transannular Michael addition. Furthermore, compound (-)-adenophorone exhibited potent neuroprotective activity in H2O2-treated SH-SY5Y and PC12 cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lena Keller, Emilia Oueis, Amninder Kaur, Nasim Safaei, Susanne H. Kirsch, Antonia P. Gunesch, Sibylle Haid, Ulfert Rand, Luka Cicin-Sain, Chengzhang Fu, Joachim Wink, Thomas Pietschmann, Rolf Mueller
Summary: A new strain of actinobacteria, Kibdelosporangium persicum sp. nov., collected from a hot desert in Iran, yielded a novel family of sesquarterpenoids (persicamidines A-E) with remarkable antiviral activity. Extensive NMR analysis revealed a hexacyclic terpenoid molecule with a modified sugar moiety on one side and a unique isourea moiety fused to the terpenoid structure. Persicamidines A-E exhibited potent activity against hCoV-229E and SARS-CoV-2 viruses in the nanomolar range, along with excellent selectivity indices, showing promise as potential drug candidates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Joscha Meiers, Jan Dastbaz, Sebastian Adam, Sari Rasheed, Susanne H. Kirsch, Peter Meiser, Peter Gross, Rolf Mueller, Alexander Titz
Summary: The highly glycosylated spike protein of SARS-CoV-2 is crucial for infection and is a target for antiviral agents and vaccines. A pineapple-derived lectin AcmJRL has been found to bind mannosides and is present in the medication bromelain. This study showed that AcmJRL binds to the spike protein of SARS-CoV-2 with a low-micromolar K-D in a carbohydrate-dependent manner.
Article
Chemistry, Multidisciplinary
Timm O. Koller, Ullrich Scheid, Teresa Koesel, Jennifer Herrmann, Daniel Krug, Helena I. M. Boshoff, Bertrand Beckert, Joanna C. Evans, Jan Schlemmer, Becky Sloan, Danielle M. Weiner, Laura E. Via, Atica Moosa, Thomas R. Ioerger, Michael Graf, Boris Zinshteyn, Maha Abdelshahid, Fabian Nguyen, Stefan Arenz, Franziska Gille, Maik Siebke, Tim Seedorf, Oliver Plettenburg, Rachel Green, Anna-Luisa Warnke, Joachim Ullrich, Ralf Warrass, Clifton E. Barry, Digby F. Warner, Valerie Mizrahi, Andreas Kirschning, Daniel N. Wilson, Rolf Mueller
Summary: The resistance of bacterial pathogens against antibiotics is a major global health threat according to the WHO. The myxobacterial antibiotic myxovalargin has been found to be highly effective against Mycobacterium tuberculosis. Detailed study of myxovalargin biosynthesis has enabled the production of this compound through fermentation. Functional genomics analysis and feeding experiments have suggested a structural revision, which was confirmed through the development of a concise total synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Microbiology
Arne Bublitz, Madita Brauer, Stefanie Wagner, Walter Hofer, Mathias Musken, Felix Deschner, Till R. Lesker, Meina Neumann-Schaal, Lena -Sophie Paul, Ulrich Nubel, Jurgen Bartel, Andreas M. Kany, Daniela Zuhlke, Steffen Bernecker, Rolf Jansen, Susanne Sievers, Katharina Riedel, Jennifer Herrmann, Rolf Mueller, Thilo M. Fuchs, Till Strowig
Summary: Clostridium difficile infections (CDIs) are a significant healthcare problem, mainly due to high rates of relapsing/recurrent CDIs (rCDIs). In this study, the antimicrobial activity of chlorotonils against C. difficile is demonstrated. Chlorotonil A (ChA) effectively inhibits disease and prevents rCDI in mice, with minimal impact on the microbiota and intestinal metabolome. ChA also accumulates in the spore and inhibits outgrowth, potentially reducing rates of rCDI. These findings suggest that chlorotonils have unique antimicrobial properties targeting critical steps in the infection cycle of C. difficile.
CELL HOST & MICROBE
(2023)
Article
Infectious Diseases
Lais Pessanha de Carvalho, Elena Niepoth, Arbreshe Mavraj-Husejni, Andrea Kreidenweiss, Jennifer Herrmann, Rolf Mueller, Tanja Knaab, Bjoern B. Burckhardt, Thomas Kurz, Jana Held
Summary: In the absence of an effective vaccine, chemotherapy remains crucial for controlling malaria. The emergence of drug-resistant parasites emphasizes the need for new antimalarial drugs with improved properties. A sandwich enzyme-linked immunosorbent assay that detects the presence of Plasmodium falciparum histidine-rich protein 2 (HRP-2) was developed as an alternative to assess the parasite reduction ratio (PRR). The assay showed comparable results to the traditional method of measuring [3H]hypoxanthine incorporation. Rating: 7/10.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Biochemistry & Molecular Biology
Yu Mi Park, Markus R. Meyer, Rolf Mueller, Jennifer Herrmann
Summary: Zebrafish larvae have been established as a suitable in vivo model for drug metabolism studies. In this study, we focused on developing mass spectrometry imaging (MSI) protocols to investigate the spatial distribution of drugs and metabolites in zebrafish larvae. By studying the metabolism of naloxone, an opioid antagonist, we found that the zebrafish larvae model showed similar metabolites as human cells and other animal models. Furthermore, we successfully obtained MS images of naloxone and its metabolites in zebrafish larvae using optimized sample preparation procedures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Sergi H. Akone, Joachim J. Hug, Amninder Kaur, Ronald Garcia, Rolf Mueller
Summary: The study reports the discovery, isolation, structure elucidation, and biological evaluation of two new bacterial sterols, nannosterols A and B, from the terrestrial myxobacterium Nannocystis sp. These nannosterols features unique modifications and chemical features, such as a secondary alcohol group at position C-15 and a terminal vicinal diol side chain at C-24-C-25, which have not been observed in bacterial sterols before. The investigation based on myxobacterial high-resolution secondary metabolome data and genomic in silico investigations revealed that nannosterols are frequently produced sterols within the myxobacterial suborder of Nannocystineae. The discovery of nannosterols provides insights into the biosynthesis and evolution of sterols by prokaryotes.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Multidisciplinary Sciences
Philip Schippers, Sari Rasheed, Yu Mi Park, Timo Risch, Lea Wagmann, Selina Hemmer, Sascha K. Manier, Rolf Mueller, Jennifer Herrmann, Markus R. Meyer
Summary: This study compared six different extraction procedures to find the most suitable one for extracting zebrafish larvae in the context of an infection model. The two-phase methods (III and IV) resulted in a lower feature count, higher peak areas of interest (MoInt), especially amino acids, and higher coefficients of variation. Adding bead homogenization increased the feature count, peak areas, and CVs. Extraction I showed higher peak areas and lower CVs than extraction II, making it the most suitable one-phase method. Extraction III and IV showed similar results, with III being easier to execute and less prone to imprecisions. Thus, extractions I and III might be chosen for future applications in zebrafish larvae metabolomics and infection models.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Zong-Jie Wang, Xiaotong Liu, Haibo Zhou, Yang Liu, Qiang Tu, Liujie Huo, Fu Yan, Rolf Mueller, Youming Zhang, Xiaokun Xu
Summary: Engineering the biosynthetic pathways of complex natural products is a significant approach to obtain derivatives with improved properties. Here, we constructed a streamlined engineered biosynthesis system of myxobacterium-derived complex polyketide disorazol in a heterologous host. The inactivation of dehydratase domains led to the production of hydroxylated derivatives, while module deletion allowed the generation of an unnatural derivative with a truncated macrolactone ring. These disorazol derivatives showed different activities against human cancer cell lines, indicating a structure-activity relationship. The PKS engineering enables structural derivatization of disorazol, facilitating the in-depth engineered biosynthesis of polyketides.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Judith Boldt, Laima Lukoseviciute, Chengzhang Fu, Matthias Steglich, Boyke Bunk, Vera Junker, Aileen Gollasch, Birte Trunkwalter, Kathrin I. Mohr, Michael Beckstette, Joachim Wink, Joerg Overmann, Rolf Mueller, Ulrich Nuebel
Summary: A better understanding of the genetic regulation of microbial compound biosynthesis can accelerate the discovery and production of new biologically active molecules. This study investigated the transcriptional dynamics of biosynthetic gene clusters (BGCs) in the myxobacterium Sorangium sp. So ce836, revealing that BGC transcription is associated with the production of natural compounds. The findings challenge the commonly held belief of preferential BGC expression under nutrient-limited conditions and highlight the need for genetic engineering tools to enhance compound yields from myxobacterial strains.
MICROBIAL BIOTECHNOLOGY
(2023)
Article
Microbiology
Yunsheng Gao, Joy Birkelbach, Chengzhang Fu, Jennifer Herrmann, Herbert Irschik, Bernd Morgenstern, Kerstin Hirschfelder, Ruijuan Li, Youming Zhang, Rolf Jansen, Rolf Mueller
Summary: Microbial secondary metabolites are abundant sources of bioactive compounds and are privileged scaffolds for the development of new drugs. Therefore, continuous discovery of novel bioactive natural products is crucial for pharmaceutical research. Myxobacteria, particularly Sorangium spp., are known for their underexploited biosynthetic potential and serve as proficient producers of such secondary metabolites. In this study, a family of natural products called disorazole Z was isolated and characterized from Sorangium cellulosum strain So ce1875, showing potent anticancer activity. Furthermore, the biosynthesis and heterologous production of disorazole Z were reported, providing potential for the development of disorazole-based anticancer drugs for clinical studies.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Franziska Fries, Andreas Kany, Sari Rasheed, Anna Hirsch, Rolf Mueller, Jennifer Herrmann
Summary: A zebrafish embryo model was established to evaluate the in vivo efficacy of potential antimicrobials, providing a novel screening platform for antibiotic discovery. Consideration of the appropriate administration route based on the physicochemical properties of tested drugs was also provided.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Carolin Blask, Juliane Schulze, Sarah Ruempel, Marie Suess, Matthias Grothe, Stefan Gross, Alexander Dressel, Rolf Mueller, Johanna Ruhnau, Antje Vogelgesang
Summary: By using acetyl-CoA-carboxylase inhibitors Soraphen A (SorA) and coenzyme A (CoA) ex vivo, the study aimed to decrease the release of proinflammatory cytokines and increase anti-inflammatory cytokine levels in PBMCs, indicating a potential application in future multiple sclerosis (MS) therapy. The analysis of cytokine production in PBMCs treated with SorA (10 or 50 nM) and CoA (600μM) showed immunomodulatory effects in MS patients, with a reduction in cytokine levels overall except for IL-2, IL-6, and IL-10.
JOURNAL OF NEUROIMMUNOLOGY
(2023)
Article
Biology
Sophia Gessner, Zela Alexandria-Mae Martin, Michael A. Reiche, Joana A. Santos, Ryan Dinkele, Atondaho Ramudzuli, Neeraj Dhar, Timothy J. de Wet, Saber Anoosheh, Dirk M. Lang, Jesse Aaron, Teng-Leong Chew, Jennifer Herrmann, Rolf Mueller, John D. McKinney, Roger Woodgate, Valerie Mizrahi, Ceslovas Venclovas, Meindert H. Lamers, Digby F. Warner
Summary: A study found that a DNA damage-inducible mutagenic gene cassette is involved in the emergence of drug resistance in Mycobacterium tuberculosis. The study also revealed the molecular composition and operation of the encoded 'mycobacterial mutasome'. These findings provide a new target for the development of adjunctive therapeutics to protect anti-TB drugs against emerging resistance.
Article
Infectious Diseases
Mariam Rima, Niels Pfennigwerth, Martina Cremanns, Katarina Cirnski, Saoussen Oueslati, Soeren G. Gatermann, Nicola d'Amelio, Jennifer Herrmann, Rolf Mueller, Thierry Naas
Summary: The development of novel antibiotics is crucial to combat the growing problem of antibiotic resistance. In this study, the activity spectrum of cystobactamids and chelocardins, two promising classes of molecules with different modes of action, was determined. These molecules showed potent activities against clinically relevant Gram-negative and Gram-positive bacteria, including multi-drug resistant strains. The findings suggest that cystobactamid CN-DM-861 and chelocardin CDCHD have interesting antibiotic activities on MDR or XDR bacteria without cross-resistance to clinically relevant antibiotics.
