Molecular Diversity Sculpted by Fungal PKS–NRPS Hybrids

Boettger, Daniela; Hertweck, Christian

doi:10.1002/cbic.201200624

Cited by 189 publications

(175 citation statements)

References 119 publications

(179 reference statements)

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“…As shown for the biosynthesis of equisetin, decalinoyl tetramic acids constitute polyketide-nonribosomal peptide hybrids (Boettger and Hertweck, 2013), which are built up from an octaketide respectively nonaketide and an amino acid. Thus, threonine can be considered as a non-alternated building block of 2.…”

Section: Resultsmentioning

confidence: 99%

Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus

et al. 2014

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A 3-decalinoyltetramic acid, for which the trivial name hymenosetin is proposed, was isolated from crude extracts of a virulent strain of the ash dieback pathogen, Hymenoscyphus pseudoalbidus (= "Chalara fraxinea"). This compound was produced only under certain culture conditions in submerged cultures of the fungus. Its planar structure was determined by NMR spectroscopy and by mass spectrometry. The absolute stereochemistry was assigned by CD spectroscopy and HETLOC data. Hymenosetin exhibited broad spectrum antibacterial and antifungal activities (including strong inhibition of MRSA, as well as moderate cytotoxic effects.So far, the metabolite proved inactive in assays for evaluation of phytotoxicity, whereas viridiol, another secondary metabolite known from H. pseudoalbidus, was regarded as phytotoxic principle of the pathogen against its host, Fraxinus excelsior. Further studies will show whether hymenosetin constitutes a defence metabolite that is produced by the pathogenic fungus to combat other microbes and fungi in the natural environment.

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Section: Resultsmentioning

confidence: 99%

Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus

et al. 2014

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“…Relatively few studies describe the identification and characterization of enzymes and pathways that give rise to sesqui-, di-and triterpene natural products in filamentous fungi. Based on literature reports and a survey in SciFinder, polyketides (PK) and non-ribosomal peptides (NRP) synthesized by thiotemplate mechanism synthetases (PKSs and NRPSs) clearly appear to be the major classes of natural products made by Ascomycota [94][95][96]. A similar survey for natural products isolated from Basidiomycota, however, returned less than 100 potentially PKS-or NRPS-derived compounds, whereas close to 500 reports (*1,000 compounds) described the isolation of terpenoids.…”

Section: Isoprenoid Biosynthetic Genes In Ascomycota and Basidiomycotamentioning

confidence: 99%

Biosynthesis of Terpenoid Natural Products in Fungi

Schmidt‐Dannert

2014

Advances in Biochemical Engineering/Biotechnology

108

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Tens of thousands of terpenoid natural products have been isolated from plants and microbial sources. Higher fungi (Ascomycota and Basidiomycota) are known to produce an array of well-known terpenoid natural products, including mycotoxins, antibiotics, antitumor compounds, and phytohormones. Except for a few well-studied fungal biosynthetic pathways, the majority of genes and biosynthetic pathways responsible for the biosynthesis of a small number of these secondary metabolites have only been discovered and characterized in the past 5-10 years. This chapter provides a comprehensive overview of the current knowledge on fungal terpenoid biosynthesis from biochemical, genetic, and genomic viewpoints. Enzymes involved in synthesizing, transferring, and cyclizing the prenyl chains that form the hydrocarbon scaffolds of fungal terpenoid natural products are systematically discussed. Genomic information and functional evidence suggest differences between the terpenome of the two major fungal phyla--the Ascomycota and Basidiomycota--which will be illustrated for each group of terpenoid natural products.

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“…Many other compounds produced by ascomycetes are toxic and are known as mycotoxins, which pose substantial threats to human food supplies and health (5). Major classes of natural products from Ascomycetes include alkaloids (6,7), terpenoids (8), polyketides (PKs) (9)(10)(11)(12), nonribosomal peptides (NRPs) (12)(13)(14), and PK-NRP hybrids (15,16). However, ribosomally synthesized and posttranslationally modified peptides (RiPPs), a rapidly growing class of natural products (17), have rarely been found in Ascomycetes.…”

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confidence: 99%

Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

Ding

Liu

Jia

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

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Production of ribosomally synthesized and posttranslationally modified peptides (RiPPs) has rarely been reported in fungi, even though organisms of this kingdom have a long history as a prolific source of natural products. Here we report an investigation of the phomopsins, antimitotic mycotoxins. We show that phomopsin is a fungal RiPP and demonstrate the widespread presence of a pathway for the biosynthesis of a family of fungal cyclic RiPPs, which we term dikaritins. We characterize PhomM as an S-adenosylmethioninedependent α-N-methyltransferase that converts phomopsin A to an N,N-dimethylated congener (phomopsin E), and show that the methyltransferases involved in dikaritin biosynthesis have evolved differently and likely have broad substrate specificities. Genome mining studies identified eight previously unknown dikaritins in different strains, highlighting the untapped capacity of RiPP biosynthesis in fungi and setting the stage for investigating the biological activities and unknown biosynthetic transformations of this family of fungal natural products.RiPP | mycotoxin | posttranslational modification | methyltransferase | biosynthesis

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Molecular Diversity Sculpted by Fungal PKS–NRPS Hybrids

Cited by 189 publications

References 119 publications

Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus

Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus

Biosynthesis of Terpenoid Natural Products in Fungi

Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

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