Filter and export

Publications

What is a Publication?
10 Publications visible to you, out of a total of 10
Mining and unearthing hidden biosynthetic potential.

Abstract (Expand)

Genetically encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Yet, these chemical mediators often evade detection, … and the discovery of novel entities is hampered by low production and high rediscovery rates. These limitations may be addressed by genome mining for biosynthetic gene clusters, thereby unveiling cryptic metabolic potential. The development of sophisticated data mining methods and genetic and analytical tools has enabled the discovery of an impressive array of previously overlooked natural products. This review shows the newest developments in the field, highlighting compound discovery from unconventional sources and microbiomes.

Authors: K. Scherlach, C. Hertweck

Date Published: 23rd Jun 2021

Publication Type: Journal

Iron Coordination Properties of Gramibactin as Model for the New Class of Diazeniumdiolate Based Siderophores.

Abstract (Expand)

Gramibactin (GBT) is an archetype for the new class of diazeniumdiolate siderophores, produced by Paraburkholderia graminis, a cereal-associated rhizosphere bacterium, for which a detailed solution … thermodynamic study exploring the iron coordination properties is reported. The acid-base behavior of gramibactin as well as its complexing ability toward Fe(3+) was studied over a wide range of pH values (2</=pH</=11). For the latter the ligand-competition method employing EDTA was used. Only two species are formed: [Fe(GBT)](-) (pH 2 to 9) and [Fe(GBT)(OH)2 ](3-) (pH>/=9). The formation of [Fe(GBT)](-) and its occurrence in real systems was confirmed by LC-HRESIMS analysis of the bacteria culture broth extract. The sequestering ability of gramibactin was also evaluated in terms of the parameters pFe and pL0.5 . Gramibactin exhibits a higher sequestering ability toward Fe(3+) than EDTA and of the same order of magnitude as hydroxamate-type microbial siderophores, but smaller than most of the catecholate-type siderophores and much higher than the most known phytosiderophores.

Authors: S. Gama, R. Hermenau, M. Frontauria, D. Milea, S. Sammartano, C. Hertweck, W. Plass

Date Published: 5th Feb 2021

Publication Type: Journal

N-Heterocyclization in Gliotoxin Biosynthesis is Catalyzed by a Distinct Cytochrome P450 Monooxygenase.

Abstract (Expand)

Gliotoxin and related epidithiodiketopiperazines (ETP) from diverse fungi feature highly functionalized hydroindole scaffolds with an array of medicinally and ecologically relevant activities. Mutation … analysis, heterologous reconstitution, and biotransformation experiments revealed that a cytochrome P450 monooxygenase (GliF) from the human-pathogenic fungus Aspergillus fumigatus plays a key role in the formation of the complex heterocycle. In vitro assays using a biosynthetic precursor from a blocked mutant showed that GliF is specific to ETPs and catalyzes an unprecedented heterocyclization reaction that cannot be emulated with current synthetic methods. In silico analyses indicate that this rare biotransformation takes place in related ETP biosynthetic pathways.

Authors: D. H. Scharf, P. Chankhamjon, K. Scherlach, J. Dworschak, T. Heinekamp, M. Roth, A. A. Brakhage, C. Hertweck

Date Published: 15th Jan 2021

Publication Type: Journal

Chemical Mediators at the Bacterial-Fungal Interface.

Abstract (Expand)

Interactions among microbes are key drivers of evolutionary progress and constantly shape ecological niches. Microorganisms rely on chemical communication to interact with each other and surrounding … organisms. They synthesize natural products as signaling molecules, antibiotics, or modulators of cellular processes that may be applied in agriculture and medicine. Whereas major insight has been gained into the principles of intraspecies interaction, much less is known about the molecular basis of interspecies interplay. In this review, we summarize recent progress in the understanding of chemically mediated bacterial-fungal interrelations. We discuss pairwise interactions among defined species and systems involving additional organisms as well as complex interactions among microbial communities encountered in the soil or defined as microbiota of higher organisms. Finally, we give examples of how the growing understanding of microbial interactions has contributed to drug discovery and hypothesize what may be future directions in studying and engineering microbiota for agricultural or medicinal purposes.

Authors: K. Scherlach, C. Hertweck

Date Published: 8th Sep 2020

Publication Type: Journal

Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens.

Abstract (Expand)

Numerous postharvest diseases have been reported that cause substantial losses of citrus fruits worldwide. Penicillium digitatum is responsible for up to 90% of production losses, and represent a problem … for worldwide economy. In order to control phytopathogens, chemical fungicides have been extensively used. Yet, the use of some artificial fungicides cause concerns about environmental risks and fungal resistance. Therefore, studies focusing on new approaches, such as the use of natural products, are getting attention. Co-culture strategy can be applied to discover new bioactive compounds and to understand microbial ecology. Mass Spectrometry Imaging (MSI) was used to screen for potential antifungal metabolites involved in the interaction between Penicillium digitatum and Penicillium citrinum. MSI revealed a chemical warfare between the fungi: two tetrapeptides, deoxycitrinadin A, citrinadin A, chrysogenamide A and tryptoquialanines are produced in the fungi confrontation zone. Antimicrobial assays confirmed the antifungal activity of the investigated metabolites. Also, tryptoquialanines inhibited sporulation of P. citrinum. The fungal metabolites reported here were never described as antimicrobials until this date, demonstrating that co-cultures involving phytopathogens that compete for the same host is a positive strategy to discover new antifungal agents. However, the use of these natural products on the environment, as a safer strategy, needs further investigation. This paper aimed to contribute to the protection of agriculture, considering health and ecological risks.

Authors: J. H. Costa, C. I. Wassano, C. F. F. Angolini, K. Scherlach, C. Hertweck, T. Pacheco Fill

Date Published: 9th Dec 2019

Publication Type: Journal

Genomics-Driven Discovery of NO-Donating Diazeniumdiolate Siderophores in Diverse Plant-Associated Bacteria.

Abstract (Expand)

Siderophores are key players in bacteria-host interactions, with the main function to provide soluble iron for their producers. Gramibactin from rhizosphere bacteria expands siderophore function and … diversity as it delivers iron to the host plant and features an unusual diazeniumdiolate moiety for iron chelation. By mutational analysis of the grb gene cluster, we identified genes (grbD and grbE) necessary for diazeniumdiolate formation. Genome mining using a GrbD-based network revealed a broad range of orthologous gene clusters in mainly plant-associated Burkholderia/Paraburkholderia species. Two new types of diazeniumdiolate siderophores, megapolibactins and plantaribactin were fully characterized. In vitro assays and in vivo monitoring experiments revealed that the iron chelators also liberate nitric oxide (NO) in plant roots. This finding is important since NO donors are considered as biofertilizers that maintain iron homeostasis and increase overall plant fitness.

Authors: R. Hermenau, J. L. Mehl, K. Ishida, B. Dose, S. J. Pidot, T. P. Stinear, C. Hertweck

Date Published: 9th Sep 2019

Publication Type: Journal

Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand system.

Abstract (Expand)

Genome mining and chemical analyses revealed that rhizosphere bacteria (Paraburkholderia graminis) produce a new type of siderophore, gramibactin, a lipodepsipeptide that efficiently binds iron with a … logbeta value of 27.6. Complexation-induced proton NMR chemical shifts show that the unusual N-nitrosohydroxylamine (diazeniumdiolate) moieties participate in metal binding. Gramibactin biosynthesis genes are conserved in numerous plant-associated bacteria associated with rice, wheat, and maize, which may utilize iron from the complex.

Authors: R. Hermenau, K. Ishida, S. Gama, B. Hoffmann, M. Pfeifer-Leeg, W. Plass, J. F. Mohr, T. Wichard, H. P. Saluz, C. Hertweck

Date Published: 1st Aug 2018

Publication Type: Journal

An antifungal polyketide associated with horizontally acquired genes supports symbiont-mediated defense in Lagria villosa beetles.

Abstract (Expand)

Microbial symbionts are often a source of chemical novelty and can contribute to host defense against antagonists. However, the ecological relevance of chemical mediators remains unclear for most … systems. Lagria beetles live in symbiosis with multiple strains of Burkholderia bacteria that protect their offspring against pathogens. Here, we describe the antifungal polyketide lagriamide, and provide evidence supporting that it is produced by an uncultured symbiont, Burkholderia gladioli Lv-StB, which is dominant in field-collected Lagria villosa. Interestingly, lagriamide is structurally similar to bistramides, defensive compounds found in marine tunicates. We identify a gene cluster that is probably involved in lagriamide biosynthesis, provide evidence for horizontal acquisition of these genes, and show that the naturally occurring symbiont strains on the egg are protective in the soil environment. Our findings highlight the potential of microbial symbionts and horizontal gene transfer as influential sources of ecological innovation.

Authors: L. V. Florez, K. Scherlach, I. J. Miller, A. Rodrigues, J. C. Kwan, C. Hertweck, M. Kaltenpoth

Date Published: 26th Jun 2018

Publication Type: Journal

Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen.

Abstract (Expand)

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by … the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defenses and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defenses such that colony collapse is unavoidable once Escovopsis infections escalate.

Authors: D. Heine, N. A. Holmes, S. F. Worsley, A. C. A. Santos, T. M. Innocent, K. Scherlach, E. H. Patrick, D. W. Yu, J. C. Murrell, P. C. Vieria, J. J. Boomsma, C. Hertweck, M. I. Hutchings, B. Wilkinson

Date Published: 7th Jun 2018

Publication Type: Journal

Two Types of Threonine-Tagged Lipopeptides Synergize in Host Colonization by Pathogenic Burkholderia Species.

Abstract (Expand)

Bacterial infections of agriculturally important mushrooms and plants pose a major threat to human food sources worldwide. However, structures of chemical mediators required by the pathogen for host … colonization and infection remain elusive in most cases. Here, we report two types of threonine-tagged lipopeptides conserved among mushroom and rice pathogenic Burkholderia species that facilitate bacterial infection of hosts. Genome mining, metabolic profiling of infected mushrooms, and heterologous expression of orphan gene clusters allowed the discovery of these unprecedented metabolites in the mushroom pathogen Burkholderia gladioli (haereogladin, burriogladin) and the plant pathogen Burkholderia glumae (haereoglumin and burrioglumin). Through targeted gene deletions, the molecular basis of lipopeptide biosynthesis by nonribosomal peptide synthetases was revealed. Surprisingly, both types of lipopeptides feature unusual threonine tags, which yield longer peptide backbones than one would expect based on the canonical colinearity of the NRPS assembly lines. Both peptides play an indirect role in host infection as biosurfactants that enable host colonization by mediating swarming and biofilm formation abilities. Moreover, MALDI imaging mass spectrometry was applied to investigate the biological role of the lipopeptides. Our results shed light on conserved mechanisms that mushroom and plant pathogenic bacteria utilize for host infection and expand current knowledge on bacterial virulence factors that may represent a new starting point for the targeted development of crop protection measures in the future.

Authors: T. Thongkongkaew, W. Ding, E. Bratovanov, E. Oueis, M. A. Garci A-Altares, N. Zaburannyi, K. Harmrolfs, Y. Zhang, K. Scherlach, R. Muller, C. Hertweck

Date Published: 18th May 2018

Publication Type: Journal

Powered by
 (v.1.15.2)
About | About ChemBioSys | Funding and Programmes | Credits
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH