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153 Publications visible to you, out of a total of 153
Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5-Lipoxygenase Inhibitors

Abstract (Expand)

The siderophore myxochelin A is a potent inhibitor of human 5-lipoxygenase (5-LO). To clarify whether the iron-chelating properties of myxochelin A are responsible for this activity, several analogues … of this compound were generated in the native producer Pyxidicoccus fallax by precursor-directed biosynthesis. Testing in a cell-free assay unveiled three derivatives with bioactivity comparable with that of myxochelin A. Furthermore, it became evident that inhibition of 5-LO by myxochelins does not correlate with their iron affinities.

Authors: J. Korp, S. Konig, S. Schieferdecker, H. M. Dahse, G. M. Konig, ,

Date Published: 13th Oct 2015

Publication Type: Not specified

Helper bacteria halt and disarm mushroom pathogens by linearizing structurally diverse cyclolipopeptides.

Abstract (Expand)

The bacterial pathogen Pseudomonas tolaasii severely damages white button mushrooms by secretion of the pore-forming toxin tolaasin, the main virulence factor of brown blotch disease. Yet, fungus-associated … helper bacteria of the genus Mycetocola (Mycetocola tolaasinivorans and Mycetocola lacteus) may protect their host by an unknown detoxification mechanism. By a combination of metabolic profiling, imaging mass spectrometry, structure elucidation, and bioassays, we found that the helper bacteria inactivate tolaasin by linearizing the lipocyclopeptide. Furthermore, we found that Mycetocola spp. impair the dissemination of the pathogen by cleavage of the lactone ring of pseudodesmin. The role of pseudodesmin as a major swarming factor was corroborated by identification and inactivation of the corresponding biosynthetic gene cluster. Activity-guided fractionation of the Mycetocola proteome, matrix-assisted laser desorption/ionization (MALDI) analyses, and heterologous enzyme production identified the lactonase responsible for toxin cleavage. We revealed an antivirulence strategy in the context of a tripartite interaction that has high ecological and agricultural relevance.

Authors: R. Hermenau, S. Kugel, A. J. Komor, C. Hertweck

Date Published: 31st Aug 2020

Publication Type: Not specified

High-density cultivation of terrestrial Nostoc strains leads to reprogramming of secondary metabolome.

Abstract (Expand)

Terrestrial symbiotic cyanobacteria of the genus Nostoc exhibit a large potential for the production of bioactive natural products of the nonribosomal peptide, polyketide and ribosomal peptide classes, … yet most of the biosynthetic gene clusters are silent under conventional cultivation conditions. In the present study, we have utilized a high-density cultivation approach recently developed for phototrophic bacteria to rapidly generate biomass of the filamentous bacteria up to a density of 400 g wet weight/L. Unexpectedly, integrated transcriptional and metabolomics studies uncovered a major reprogramming of the secondary metabolome of two Nostoc strains at high culture density and a governing effect of extracellular signals in this process. The holistic approach enabled capturing and structural elucidation of novel variants of anabaenopeptin including one congener with potent allelopathic activity against a strain isolated from the same habitat. The study provides a snapshot on the role of cell-type specific expression for the formation of natural products in cyanobacteria.Importance Terrestrial filamentous cyanobacteria are a largely untapped source of small molecular natural products. Exploitation of the phototrophic organisms is hampered by their slow growth and the requirement of photobioreactors. The current study not only demonstrates the suitability of a recently developed two-tier vessel cultivation approach for the rapid generation of biomass of Nostoc strains but also demonstrates a pronounced up regulation of high value natural products at ultra-high culture densities. The study provides new guidelines for high-throughput screening and exploitation of small molecule natural products and can facilitate the discovery new bioactive products from terrestrial cyanobacteria.

Authors: A. Guljamow, M. Kreische, K. Ishida, A. Liaimer, B. Altermark, L. Bahr, C. Hertweck, R. Ehwald, E. Dittmann

Date Published: 25th Sep 2017

Publication Type: Not specified

High-throughput quantification of more than 100 primary- and secondary-metabolites, and phytohormones by a single solid-phase extraction based sample preparation with analysis by UHPLC-HESI-MS/MS

Abstract (Expand)

BACKGROUND: Plant metabolites are commonly functionally classified, as defense- or growth-related phytohormones, primary and specialized metabolites, and so forth. Analytical procedures for the … quantifications of these metabolites are challenging because the metabolites can vary over several orders of magnitude in concentrations in the same tissues and have very different chemical characteristics. Plants clearly adjust their metabolism to respond to their prevailing circumstances in very sophisticated ways that blur the boundaries among these functional or chemically defined classifications. But if plant biologists want to better understand the processes that are important for a plant's adaptation to its environment, procedures are needed that can provide simultaneous quantifications of the large range of metabolites that have the potential to play central roles in these adjustments in a cost and time effective way and with a low sample consumption. RESULTS: Here we present a method that combines well-established methods for the targeted analysis of phytohormones, including jasmonates, salicylic acid, abscisic acid, gibberellins, auxins and cytokinins, and extends it to the analysis of inducible and constitutive defense compounds, as well as the primary metabolites involved in the biosynthesis of specialized metabolites and responsible for nutritional quality (e.g., sugars and amino acids). The method is based on a single extraction of 10-100 mg of tissue and allows a broad quantitative screening of metabolites optimized by their chemical characteristics and concentrations, thereby providing a high throughput analysis unbiased by the putative functional attributes of the metabolites. The tissues of Nicotiana attenuata which accumulate high levels of nicotine and diterpene glycosides, provide a challenging matrix that thwarts quantitative analysis; the analysis of various tissues of this plant are used to illustrate the robustness of the procedure. CONCLUSIONS: The method described has the potential to unravel various, until now overlooked interactions among different sectors of plant metabolism in a high throughput manner. Additionally, the method could be particularly beneficial as screening method in forward genetic approaches, as well as for the investigation of plants from natural populations that likely differ in metabolic traits.

Authors: , C. Brutting, , M. Kallenbach

Date Published: 31st May 2016

Publication Type: Not specified

Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity.

Abstract (Expand)

Proinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes … biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli and S. aureus each stimulate predominantly proinflammatory 5-lipoxygenase (LOX) and cyclooxygenase pathways (i.e., leukotriene B4 and prostaglandin E2) in M1 macrophages. These pathogens stimulate M2 macrophages to produce SPMs including resolvin D2 (RvD2), RvD5, and maresin-1. E. coli activates M2 macrophages to translocate 5-LOX and 15-LOX-1 to different subcellular locales in a Ca(2+)-dependent manner. Neither attenuated nor non-pathogenic E. coli mobilize Ca(2+) or activate LOXs, rather these bacteria stimulate prostaglandin production. RvD5 is more potent than leukotriene B4 at enhancing macrophage phagocytosis. These results indicate that M1 and M2 macrophages respond to pathogenic bacteria differently, producing either leukotrienes or resolvins that further distinguish inflammatory or pro-resolving phenotypes.

Authors: O. Werz, J. Gerstmeier, S. Libreros, X. De la Rosa, M. Werner, P. C. Norris, N. Chiang, C. N. Serhan

Date Published: No date defined

Publication Type: Not specified

Humudifucol and Bioactive Prenylated Polyphenols from Hops (Humulus lupulus cv. "Cascade")

Abstract (Expand)

Humulus lupulus (hop plant) has long been used in traditional medicine as a sedative and antimicrobial agent. More recently, attention has been devoted to the phytoestrogenic activity of the plant … extracts as well as to the anti-inflammatory and chemopreventive properties of the prenylated chalcones present. In this study, an Italian sample of H. lupulus cv. "Cascade" has been investigated and three new compounds [4-hydroxycolupulone (6), humudifucol (7) and cascadone (8)] have been purified and identified by means of NMR spectroscopy along with four known metabolites. Notably, humudifucol (7) is the first prenylated dimeric phlorotannin discovered in nature. Because structurally related phloroglucinols from natural sources were found previously to inhibit microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), the isolated compounds were evaluated for their bioactivity against these pro-inflammatory target proteins. The prenylated chalcone xanthohumol inhibited both enzymes at low muM concentrations.

Authors: M. Forino, , G. Chianese, L. Santagostini, , C. Weinigel, S. Rummler, G. Fico, , O. Taglialatela-Scafati

Date Published: 27th Feb 2016

Publication Type: Not specified

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