Review
Biochemistry & Molecular Biology
Mariana Rodriguez-Cisneros, Leslie Mariana Morales-Ruiz, Anuar Salazar-Gomez, Fernando Uriel Rojas-Rojas, Paulina Estrada-de los Santos
Summary: Due to the increase in multidrug-resistant microorganisms, there is a need to investigate novel or more efficient antimicrobial compounds. The World Health Organization has identified priority multidrug-resistant bacteria requiring new antibiotics. Burkholderia, a group of species known for producing antimicrobials, produces a wide range of compounds including N-containing heterocycles, volatile organic compounds, and bacteriocins. Some of these compounds have potential as antimicrobials, anticancer, or antitumor agents. This review explores the antimicrobial compounds produced by Burkholderia, with a focus on those tested in vitro for antimicrobial activity and novel compounds discovered through genome-guided approaches.
Article
Biochemistry & Molecular Biology
Zinnet Sevval Aksoyalp, Aybala Temel, Betul Rabia Erdogan
Summary: Iron plays an important role in metabolic functions in organisms and its interaction with the microbiota influences susceptibility to infections. Imbalances in iron levels can affect the composition of the microbiota, and understanding these interactions is important for understanding the pathogenesis of infectious and metabolic diseases and developing effective preventive and therapeutic strategies.
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Bruce E. Holbein, M. Trisha C. Ang, David S. Allan, Wangxue Chen, Christian Lehmann
Summary: The iron dependence of antibiotic-resistant microbes can be exploited broadly, as iron withdrawal enhances antibiotic activity and suppresses growth of resistant microbial survivors. Novel anti-microbial iron chelators, such as DIBI, show potential in enhancing antibiotic efficacy against resistant microbes.
ENVIRONMENTAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Organic
Anna R. Kaplan, William M. Wuest
Summary: Iron is a vital nutrient for most living organisms, but acquiring it can be challenging for many, including bacteria. Bacteria often use siderophores to chelate extracellular iron, with pathogenic species like Pseudomonas aeruginosa producing specific siderophores to regulate iron uptake. Previous research showed that certain pyochelin biosynthetic shunt products can enhance the growth of P. aeruginosa in iron-depleted conditions when prechelated with iron. This study explores the physicochemical and biological properties of non-native oxygen counterparts to these metabolites.
TETRAHEDRON LETTERS
(2021)
Article
Microbiology
Guadalupe C. Barrera-Galicia, Hector A. Peniche-Pavia, Juan Jose Pena-Cabriales, Sergio A. Covarrubias, Jose A. Vera-Nunez, John P. Delano-Frier
Summary: Several Burkholderia sensu lato strains were isolated from the rhizosphere of maize plants in central Mexico, showing inhibition against pathogenic Fusarium fungi, potentially due to their siderophore synthesis. This study highlights the chemical diversity of Burkholderia sensu lato bacteria and their capacity to combat Fusarium-related infections.
Article
Medicine, Research & Experimental
Michela Asperti, Luca Cantamessa, Magdalena Gryzik, Mattia Bugatti, Silvia Codenotti, Andrea Denardo, William Vermi, Alessandro Fanzani, Maura Poli
Summary: Rhabdomyosarcoma (RMS) is an aggressive rare neoplasm that requires new therapies. This study investigated the effect of iron modulation on RMS and found that both iron supplementation and iron chelation significantly inhibited tumor growth.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Review
Medicine, Research & Experimental
Jian Zhang, Hai Zhao, Gang Yao, Penghai Qiao, Longfei Li, Shuguang Wu
Summary: Iron is an essential trace element for living organisms, but iron overload can lead to osteoporosis. Iron chelators have therapeutic effects on iron overload-induced osteoporosis and may also be used for treating bone loss caused by other factors. Iron chelators have different effects on bone cells, stimulating osteogenic differentiation in osteoblast lineage cells and inhibiting osteoclast differentiation. Antioxidant capability and fibroblast growth factor 23 are also involved in the osteoprotective effects of iron chelators.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Evan M. F. Shepherdson, Marie A. Elliot
Summary: Streptomyces bacteria have complex life cycles and remarkable metabolic capabilities. Their recently discovered exploration ability allows them to successfully compete with other microbes. Nutrient availability affects exploration rates and metabolic output, with glycerol dramatically increasing exploration rates. Different siderophores play different roles in exploration, and the alternative siderophore foroxymithine is more important than desferrioxamine during coculture.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
O. Yu. Selyutina, P. A. Kononova, V. E. Koshman, E. A. Shelepova, M. Gholam Azad, R. Afroz, M. Dharmasivam, Paul V. Bernhardt, N. E. Polyakov, D. R. Richardson
Summary: Ascorbate-driven redox cycling enhances the anti-proliferative activity of Dp44mT and Emodin.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Chemistry, Medicinal
Katerina Bendova, Vladislav Raclavsky, Radko Novotny, Dominika Luptakova, Miroslav Popper, Zbynek Novy, Marian Hajduch, Milos Petrik
Summary: Bacteria from the Burkholderia cepacia complex are generally considered non-pathogenic, but can cause serious infections in immunocompromised patients. This study developed a radiolabeled siderophore, ORNB, and demonstrated its effectiveness in positron emission tomography imaging for diagnosing Burkholderia infections. The radiolabeled complex showed optimal characteristics in vitro and accumulated at the site of infection in animal models. The results suggest that [Ga-68]-Ga-ORNB is a promising tool for diagnosing, monitoring, and evaluating therapeutic response to B. cepacia complex infection.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Forestry
Stavroula Rapti, Stamatis Boyatzis, Shayne Rivers, Athanasios Velios, Anastasia Pournou
Summary: This study investigated the potential of desferrioxamine B (DFO-B) as a chelator for removing ferric oxides/hydroxy-oxides from cultural heritage wooden substrates. The results showed that the alkaline hydrogel (pH 8.6) was the most effective formulation, followed by the acidic hydrogel (pH 6.5) and DFO-B ethanol gel. The DFO-B ethanol gels also showed potential as alternatives to hydrogels for water-sensitive cultural heritage substrates.
Review
Biotechnology & Applied Microbiology
Mohit Singh Rana, Sanjeev Kumar Prajapati
Summary: Iron is crucial for microalgae growth as it is required for maintaining photosynthetic and metabolic reactions. The limited bioavailability of iron is a significant challenge for algal-biotechnology industries. Different mechanisms of iron uptake by microalgae and cyanobacteria are discussed, along with recent attempts to improve microalgae growth through chelated iron and iron nanoparticle supplementation. The judicious supplementation of iron for commercial applications is also highlighted in the review.
ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
(2021)
Review
Biochemistry & Molecular Biology
Elvira Crescenzi, Antonio Leonardi, Francesco Pacifico
Summary: The review focuses on the different roles of NGAL in the tumor microenvironment and in cancer senescence-associated secretory phenotype (SASP), highlighting the most crucial functions that could be eventually targetable in cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Cassidy Scott, Gaurav Arora, Kayle Dickson, Christian Lehmann
Summary: Iron is essential in biochemical pathways for both humans and pathogens. In local infections, restricting iron availability can reduce reactive oxygen species and bacterial growth. Therapeutic use of iron chelators to induce iron deprivation shows potential in treating infections.
Article
Chemistry, Multidisciplinary
Anastasia E. Behar, Laurent Sabater, Maria Baskin, Christelle Hureau, Galia Maayan
Summary: The study introduces a water-soluble peptidomimetic chelator, P3, that selectively removes Cu2+ from Cu-Aβ and prevents the formation of ROS, showing potential advantages in the treatment of AD.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Pierre Stallforth, Maria Mittag, Axel A. Brakhage, Christian Hertweck, Ute A. Hellmich
Summary: Interactions between microorganisms are often mediated by specialized metabolites, which can be subject to community-dependent modifications in complex microbiomes. Chemical and biological tools can shed light on this poorly understood aspect of chemical ecology. Loss-of-function modifications are abundant, while gain-of-function modifications are underexplored but play an important role in microbial interactions, presenting great potential for our understanding of microbial interactions and targeted interference with microbial signaling.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Felix Trottmann, Jonas Fiedler, Keishi Ishida, Mie Ishida-Ito, Rory F. Little, Christian Hertweck
Summary: Novel malleicyprol congeners with different chain lengths were discovered, and it was found that medium-sized fatty acids serve as the starter units for their biosynthesis, catalyzed by the enzyme BurM. Further study on the function and role of BurM could potentially lead to the development of enzyme inhibitors as novel antivirulence therapeutics against BP pathogens.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hannah Buettner, Johannes Hoerl, Jana Krabbe, Christian Hertweck
Summary: Through comparative genome analysis and metabolic profiling, researchers found that Luteibacter anthropi has a higher biosynthetic potential and a unique NRPS gene coding for the biosynthesis of a metallophore compared to other bacteria in the same genus. They identified a new family of salicylate-derived nonribosomal peptides named anthrochelins A-D, which feature a C-terminal homocysteine tag introduced during peptide termination. Mutational analyses revealed the involvement of a cytochrome P450 monooxygenase in oxazole formation. Bioassays showed that anthrochelin significantly promotes the growth of L. anthropi in the presence of low and high copper concentrations, which are important during infections.
Article
Biochemistry & Molecular Biology
Ricarda Freke, Bjoern Heinemann, Samuel Edward Hakim, Claus-Peter Witte, Marco Herde, Tatjana M. Hildebrandt, Jakob Franke
Summary: Plants of the Allium genus produce S-alk(en)yl cysteine sulfoxides as flavor precursors, with two major representatives being isoalliin and propiin. It was previously unclear where the propyl group of propiin originated from. This study used untargeted metabolomics approach in chive seedlings to track the incorporation of carbon derived from valine in isoalliin and propiin. The findings provide new insights into the biosynthetic pathways of flavor precursors in Allium species.
Article
Biochemistry & Molecular Biology
Ingrid Richter, Philipp Wein, Zerrin Uzum, Claire E. Stanley, Jana Krabbe, Evelyn M. Molloy, Nadine Moebius, Iuliia Ferling, Falk Hillmann, Christian Hertweck
Summary: As a symbiotic partner of the fungus Rhizopus microsporus, the bacterium Mycetohabitans rhizoxinica faces challenges in evading the host's defense mechanisms. The role of a transcription activator-like (TAL) effector released by the endobacteria as an essential symbiosis factor has been discovered.
Article
Chemistry, Multidisciplinary
Ling Chuang, Shenyu Liu, Jakob Franke
Summary: A biosynthetic pathway for the modification of already cyclized tirucallane triterpenoids in Sapindales plants is discovered, in which a cytochrome P450 monooxygenase and two isomerases control the bifurcation between different plant triterpenoid classes. These enzymes are crucial for the biotechnological production of various triterpenoids.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Martin Klapper, Alexander Huebner, Anan Ibrahim, Ina Wasmuth, Maxime Borry, Veit G. Haensch, Shuaibing Zhang, Walid K. Al-Jammal, Harikumar Suma, James A. Fellows Yates, Jasmin Frangenberg, Irina M. Velsko, Somak Chowdhury, Rosa Herbst, Evgeni Bratovanov, Hans-Martin Dahse, Therese Horch, Christian Hertweck, Manuel Ramon Gonzalez Morales, Lawrence Guy Straus, Ivan Vilotijevic, Christina Warinner, Pierre Stallforth
Summary: Major advances in ancient DNA research have allowed access to paleogenomic diversity, however, the functions and capabilities of this genetic material remain largely unknown. In this study, dental calculus samples from ancient humans were examined, leading to the discovery of a biosynthetic gene cluster that produces previously unknown metabolites called paleofurans. This demonstrates the possibility of obtaining natural products from ancient organisms and opens up new opportunities for exploration in this field.
Article
Plant Sciences
Sara Leite Dias, Adriana Garibay-Hernandez, Fabian Leon Brendel, Benjamin Gabriel Chavez, Elena Brueckner, Hans-Peter Mock, Jakob Franke, John Charles D'Auria
Summary: A new method for monitoring specialized metabolites in barley and lupins was developed and validated using fluorescence detection. The method offers accurate and sensitive chromatographic separation and detection, providing an accessible alternative to LC-MS techniques for routine screening.
Article
Biochemistry & Molecular Biology
Marion Herisse, Keishi Ishida, Jordan Staiger-Creed, Louise Judd, Spencer J. Williams, Benjamin P. Howden, Timothy P. Stinear, Hans-Martin Dahse, Kerstin Voigt, Christian Hertweck, Sacha J. Pidot
Summary: Nocardia are opportunistic human pathogens that cause difficult to treat infections. However, little is known about their involvement in the pathogenesis and the natural products they produce. In this study, a new cytotoxic and antifungal polyene called terpenomycin was discovered in a human pathogenic Nocardia terpenica isolate. The biosynthetic pathway and unique features of terpenomycin were revealed, and a mutant library helped identify a terpenomycin-null mutant. These findings highlight the potential of neglected actinomycetes as producers of diverse bioactive molecules.
ACS CHEMICAL BIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Hajo Kries, Felix Trottmann, Christian Hertweck
Summary: Enzymes are increasingly recognized as valuable biocatalysts in synthetic chemistry. Many novel biocatalysts have emerged from the study of secondary metabolism, where rare and unusual reactions take place. In this review, we explore biocatalysts that address various synthetic challenges, including cyclization, C-H functionalization, and cross-coupling, among others, offering unique opportunities for green chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Mandy D. Mlotek, Benjamin Dose, Christian Hertweck
Summary: This study identifies a novel biosynthetic pathway for isothiocyanate natural products, which involves the catalytic transfer of sulfur onto isonitriles by rhodanese-like enzymes in bacteria. It not only elucidates an elusive step in bacterial isothiocyanate biosynthesis but also reveals a new function of rhodanese-like enzymes in specialized metabolism.
Article
Biochemistry & Molecular Biology
Eike Schafer, Paula S. Seibold, Stefan Bartram, Felix Trottmann, Veit G. Haensch, Markus Gressler, Andrew R. Chadeayne, Christian Hertweck, Sarah E. O'Connor, Dirk Hoffmeister
Summary: This study identified several compounds present in various Psilocybe species, including cubebol, β-copaene, δ-cadinene, and germacrene D, through fluorescence staining and transgenic techniques. The results also revealed the presence of related enzymes encoded by CubA in multiple Psilocybe species.
Article
Microbiology
Philipp Wein, Katharina Dornblut, Sebastian Herkersdorf, Thomas Krueger, Evelyn M. Molloy, Axel A. Brakhage, Dirk Hoffmeister, Christian Hertweck
Summary: The soft rot pathogen Janthinobacterium agaricidamnosum releases jagaricin, a membrane-disrupting lipopeptide. However, this toxin alone cannot explain the rapid decay of button mushrooms. In this study, we found that secretion systems, specifically T2SS and T3SS, play a crucial role in soft rot disease by secreting lytic enzymes and putative effector proteins.
Article
Chemistry, Multidisciplinary
Sebastian Goetze, Raghav Vij, Katja Burow, Nicola Thome, Lennart Urbat, Nicolas Schlosser, Sebastian Pflanze, Rita Mueller, Veit G. Haensch, Kevin Schlabach, Leila Fazlikhani, Grit Walther, Hans-Martin Dahse, Lars Regestein, Sascha Brunke, Bernhard Hube, Christian Hertweck, Philipp Franken, Pierre Stallforth
Summary: Investigating the ecological context of microbial predator-prey interactions can help identify micro-organisms that produce secondary metabolites to evade predation or kill predators. Genomic analysis and molecular biology methods can be used to identify biosynthetic gene clusters that yield new antimicrobials to combat the antimicrobial crisis. In this study, the keanumycins were identified as nonribosomal peptides that enable Pseudomonas bacteria to evade amoebal predation and exhibit strong antifungal activity. The chemical structures of the keanumycins were fully elucidated, and the genome-wide microarray analysis shed light on the mode-of-action of keanumycin A.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Microbiology
Ingrid Richter, Zerrin Uzum, Philipp Wein, Evelyn M. Molloy, Nadine Moebius, Timothy P. Stinear, Sacha J. Pidot, Christian Hertweck
Summary: The bacterial endosymbiont Mycetohabitans rhizoxinica in the phytopathogenic fungus Rhizopus microsporus plays a crucial role in fungal reproduction by secreting T3SS effectors, AWR peptide and TAL effectors. The absence of these effectors significantly reduces fungal sporulation, while their presence allows successful colonization of the fungus. This study provides insights into the control of fungal physiology by prokaryotic symbionts.
