B2

Overview

Mechanisms of Bacteria-triggered Activation of Fungal Silent Gene Clusters and Impact of Produced Compounds on Microorganisms

SEEK ID: https://data.chembiosys.de/projects/9

Public web page: Not specified

Organisms: Saccharomyces cerevisiae, Streptomyces rapamycinicus, Aspergillus nidulans, Aspergillus fumigatus

PALs: No PALs for this Project

Project created: 29th Sep 2014

Related items

12 hidden items
N-Heterocyclization in Gliotoxin Biosynthesis is Catalyzed by a Distinct Cytochrome P450 Monooxygenase.
B1, B2

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

Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus.
B2, INF

Abstract (Expand)

BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent … carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli. CONCLUSIONS: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.

Authors: R. P. de Vries, R. Riley, A. Wiebenga, G. Aguilar-Osorio, S. Amillis, C. A. Uchima, G. Anderluh, M. Asadollahi, M. Askin, K. Barry, E. Battaglia, O. Bayram, T. Benocci, S. A. Braus-Stromeyer, C. Caldana, D. Canovas, G. C. Cerqueira, F. Chen, W. Chen, C. Choi, A. Clum, R. A. Dos Santos, A. R. Damasio, G. Diallinas, T. Emri, E. Fekete, M. Flipphi, S. Freyberg, A. Gallo, C. Gournas, R. Habgood, M. Hainaut, M. L. Harispe, B. Henrissat, K. S. Hilden, R. Hope, A. Hossain, E. Karabika, L. Karaffa, Z. Karanyi, N. Krasevec, A. Kuo, H. Kusch, K. LaButti, E. L. Lagendijk, A. Lapidus, A. Levasseur, E. Lindquist, A. Lipzen, A. F. Logrieco, A. MacCabe, M. R. Makela, I. Malavazi, P. Melin, V. Meyer, N. Mielnichuk, M. Miskei, A. P. Molnar, G. Mule, C. Y. Ngan, M. Orejas, E. Orosz, J. P. Ouedraogo, K. M. Overkamp, H. S. Park, G. Perrone, F. Piumi, P. J. Punt, A. F. Ram, A. Ramon, S. Rauscher, E. Record, D. M. Riano-Pachon, V. Robert, J. Rohrig, R. Ruller, A. Salamov, N. S. Salih, R. A. Samson, E. Sandor, M. Sanguinetti, T. Schutze, K. Sepcic, E. Shelest, G. Sherlock, V. Sophianopoulou, F. M. Squina, H. Sun, A. Susca, R. B. Todd, A. Tsang, S. E. Unkles, N. van de Wiele, D. van Rossen-Uffink, J. V. Oliveira, T. C. Vesth, J. Visser, J. H. Yu, M. Zhou, M. R. Andersen, D. B. Archer, S. E. Baker, I. Benoit, A. A. Brakhage, G. H. Braus, R. Fischer, J. C. Frisvad, G. H. Goldman, J. Houbraken, B. Oakley, I. Pocsi, C. Scazzocchio, B. Seiboth, P. A. vanKuyk, J. Wortman, P. S. Dyer, I. V. Grigoriev

Date Published: 16th Feb 2017

Publication Type: Not specified

Regulation and Role of Fungal Secondary Metabolites.
B2

Abstract (Expand)

Fungi have the capability to produce a tremendous number of so-called secondary metabolites, which possess a multitude of functions, e.g., communication signals during coexistence with other microorganisms, … virulence factors during pathogenic interactions with plants and animals, and in medical applications. Therefore, research on this topic has intensified significantly during the past 10 years and thus knowledge of regulatory mechanisms and the understanding of the role of secondary metabolites have drastically increased. This review aims to depict the complexity of all the regulatory elements involved in controlling the expression of secondary metabolite gene clusters, ranging from epigenetic control and signal transduction pathways to global and specific transcriptional regulators. Furthermore, we give a short overview on the role of secondary metabolites, focusing on the interaction with other microorganisms in the environment as well as on pathogenic relationships.

Authors: J. Macheleidt, D. J. Mattern, J. Fischer, T. Netzker, J. Weber, V. Schroeckh, V. Valiante, A. A. Brakhage

Date Published: 13th Oct 2016

Publication Type: Not specified

Bacteria induce pigment formation in the basidiomycete Serpula lacrymans
B05, B2, INF

Abstract (Expand)

Basidiomycete fungi are characterized ecologically for their vital functional role in ecosystem carbon recycling and chemically for their capacity to produce a diverse array of small molecules. … Chromophoric natural products derived from the quinone precursor atromentin, such as variegatic acid and involutin, have been shown to function in redox cycling. Yet, in the context of an inter-kingdom natural system these pigments are still elusive. Here, we co-cultured the model saprotrophic basidiomycete Serpula lacrymans with an ubiquitous terrestrial bacterium, either Bacillus subtilis, Pseudomonas putida, or Streptomyces iranensis. For each, there was induction of the gene cluster encoding a non-ribosomal peptide synthetase-like enzyme (atromentin synthetase) and an aminotransferase which together produce atromentin. Correspondingly during co-culturing there was an increase in secreted atromentin-derived pigments, i.e., variegatic, xerocomic, isoxerocomic and atromentic acid. Bioinformatic analyses from 14 quinone synthetase genes, twelve of which are encoded in a cluster, identified a common promoter motif indicating a general regulatory mechanism for numerous basidiomycetes. This article is protected by copyright. All rights reserved.

Editor:

Date Published: 5th Oct 2016

Publication Type: Not specified

An Iterative O-Methyltransferase Catalyzes 1,11-Dimethylation of Aspergillus fumigatus Fumaric Acid Amides.
B05, B2, B6

Abstract (Expand)

S-adenosyl-l-methionine (SAM)-dependent methyltransfer is a common biosynthetic strategy to modify natural products. We investigated the previously uncharacterized Aspergillus fumigatus methyltransferase … FtpM, which is encoded next to the bimodular fumaric acid amide synthetase FtpA. Structure elucidation of two new A. fumigatus natural products, the 1,11-dimethyl esters of fumaryl-l-tyrosine and fumaryl-l-phenylalanine, together with ftpM gene disruption suggested that FtpM catalyzes iterative methylation. Final evidence that a single enzyme repeatedly acts on fumaric acid amides came from an in vitro biochemical investigation with recombinantly produced FtpM. Size-exclusion chromatography indicated that this methyltransferase is active as a dimer. As ftpA and ftpM homologues are found clustered in other fungi, we expect our work will help to identify and annotate natural product biosynthesis genes in various species.

Authors: D. Kalb, T. Heinekamp, S. Schieferdecker, M. Nett, A. A. Brakhage, D. Hoffmeister

Date Published: 22nd Jul 2016

Publication Type: Not specified

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