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7 Publications visible to you, out of a total of 7
Induced Chemical Defense of a Mushroom by a Double-Bond-Shifting Polyene Synthase.

Abstract (Expand)

The antilarval mushroom polyenes 18-methyl-19-oxoicosaoctaenoic acid and 20-methyl-21-oxodocosanonaenoic acid appear in response to injury of the mycelium of the stereaceous mushroom BY1. We identified … a polyketide synthase (PPS1) which belongs to a hitherto completely uncharacterized clade of polyketide synthases. Expression of the PPS1 gene is massively upregulated following mycelial damage. The synthesis of the above polyenes was reconstituted in the mold Aspergillus niger as a heterologous host. This demonstrates that PPS1 1) synchronously produces branched-chain polyketides of varied lengths, and 2) catalyzes the unprecedented shift of eight or nine double bonds. This study represents the first characterization of a reducing polyketide synthase from a mushroom. We also show that injury-induced de novo synthesis of polyketides is a fungal response strategy.

Authors: P. Brandt, M. Garcia-Altares, M. Nett, C. Hertweck, D. Hoffmeister

Date Published: 26th Apr 2017

Publication Type: Not specified

Myxochelin-Inspired 5-Lipoxygenase Inhibitors: Synthesis and Biological Evaluation

Abstract (Expand)

A total of 48 analogues of the natural product myxochelin A were prepared and evaluated for their inhibitory effects on human 5-lipoxygenase in both cell-free and cell-based assays. Structure-activity … relationship analysis revealed that the secondary alcohol function and only chiral center of myxochelin A is not required for biological activity. By expanding the diaminoalkane linker of the two aromatic residues it was possible to generate a myxochelin derivative with superior activity against 5-lipoxygenase in intact cells.

Authors: S. Schieferdecker, S. Konig, S. Pace, O. Werz, M. Nett

Date Published: 23rd Nov 2016

Publication Type: Not specified

Siderophores as molecular tools in medical and environmental applications

Abstract (Expand)

Almost all life forms depend on iron as an essential micronutrient that is needed for electron transport and metabolic processes. Siderophores are low-molecular-weight iron chelators that safeguard the … supply of this important metal to bacteria, fungi and graminaceous plants. Although animals and the majority of plants do not utilise siderophores and have alternative means of iron acquisition, siderophores have found important clinical and agricultural applications. In this review, we will highlight the different uses of these iron-chelating molecules.

Authors: , H. Kage,

Date Published: 6th Aug 2016

Publication Type: Not specified

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

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

Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining

Abstract (Expand)

Photoreactive siderophores have a major impact on the growth of planktonic organisms. To date, these molecules have mainly been reported from marine bacteria, although evidence is now accumulating that … some terrestrial bacteria also harbor the biosynthetic potential for their production. In this paper, we describe the genomics-driven discovery and characterization of variochelins, lipopeptide siderophores from the bacterium Variovorax boronicumulans, which thrives in soil and freshwater habitats. Variochelins are different from most other lipopeptide siderophores in that their biosynthesis involves a polyketide synthase. We demonstrate that the ferric iron complex of variochelin A possesses photoreactive properties and present the MS-derived structures of two degradation products that emerge upon light exposure.

Authors: , S. Schieferdecker, K. Athanasopoulou, I. Seccareccia,

Date Published: 29th Mar 2016

Publication Type: Not specified

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

Myxochelins target human 5-lipoxygenase

Abstract (Expand)

Extracts of the predatory myxobacterium Pyxidicoccus fallax HKI 727 showed antiproliferative effects on leukemic K-562 cells. Bioactivity-guided fractionation led to the isolation of the bis-catechol … myxochelin A and two new congeners. The biosynthetic origin of myxochelins C and D was confirmed by feeding studies with isotopically labeled precursors. Pharmacological testing revealed human 5-lipoxygenase (5-LO) as a molecular target of the myxochelins. In particular, myxochelin A efficiently inhibited 5-LO activity with an IC50 of 1.9 muM and reduced the proliferation of K-562 cells at similar concentrations.

Authors: S. Schieferdecker, S. Konig, , H. M. Dahse, ,

Date Published: 16th Feb 2015

Publication Type: Not specified

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