A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

Wick, Jonas; Heine, Daniel; Lackner, Gerald; Misiek, Mathias; Tauber, James P.; Jagusch, Hans; Hertweck, Christian; Hoffmeister, Dirk

doi:10.1128/aem.03168-15

Cited by 33 publications

(52 citation statements)

References 57 publications

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“…84,85 Substrate promiscuity was also reported for the halogenation of the mushroom toxin melleolide F ( 19 ) at the resorcylic acid ring by each of the five different FDHs identified in the mushroom cDNA. 86 …”

Section: Flavin-dependent Halogenasesmentioning

confidence: 99%

Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse

et al. 2017

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Naturally produced halogenated compounds are ubiquitous across all domains of life where they perform a multitude of biological functions and adopt a diversity of chemical structures. Accordingly, a diverse collection of enzyme catalysts to install and remove halogens from organic scaffolds has evolved in nature. Accounting for the different chemical properties of the four halogen atoms (fluorine, chlorine, bromine, and iodine) and the diversity and chemical reactivity of their organic substrates, enzymes performing biosynthetic and degradative halogenation chemistry utilize numerous mechanistic strategies involving oxidation, reduction, and substitution. Biosynthetic halogenation reactions range from simple aromatic substitutions to stereoselective C-H functionalizations on remote carbon centers and can initiate the formation of simple to complex ring structures. Dehalogenating enzymes, on the other hand, are best known for removing halogen atoms from man-made organohalogens, yet also function naturally, albeit rarely, in metabolic pathways. This review details the scope and mechanism of nature’s halogenation and dehalogenation enzymatic strategies, highlights gaps in our understanding, and posits where new advances in the field might arise in the near future.

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Section: Flavin-dependent Halogenasesmentioning

confidence: 99%

Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse

et al. 2017

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“…The FDH MibH was recently discovered and found to chlorinate a lanthipeptide (~1kD) (74). Several FDHs, including Rdc2/RadH (59), CazI (61), and Bmp5 (58), have been found to halogenate free phenol-containing compounds (63) (Fig. 4A, 6, 11, 12 ).…”

Section: Flavin-dependent Halogenases (Fdhs)mentioning

confidence: 99%

Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis

Andorfer

Lewis

2018

Annu. Rev. Biochem.

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Flavin dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes has been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Mutations throughout FDH structures have contributed to all of these advances. More recent studies have sought to rationalize the impact of these mutations on FDH function and to identify new FDHs to deepen our understanding of this enzyme class and to expand their utility for biocatalytic applications.

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“…Moreover, no gene models of non-melanized species were included in one of these two clusters. To the best of our knowledge this is the first report for the duplication of the melanin pathway in ascomycetous fungi, although the redundancy of important secondary metabolite genes was reported previously [87, 88]. Still, the products of many of the secondary metabolite key enzymes and clusters remain unresolved.…”

Section: Discussionmentioning

confidence: 81%

Globally distributed root endophyte Phialocephala subalpina links pathogenic and saprophytic lifestyles

et al. 2016

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BackgroundWhereas an increasing number of pathogenic and mutualistic ascomycetous species were sequenced in the past decade, species showing a seemingly neutral association such as root endophytes received less attention. In the present study, the genome of Phialocephala subalpina, the most frequent species of the Phialocephala fortinii s.l. – Acephala applanata species complex, was sequenced for insight in the genome structure and gene inventory of these wide-spread root endophytes.ResultsThe genome of P. subalpina was sequenced using Roche/454 GS FLX technology and a whole genome shotgun strategy. The assembly resulted in 205 scaffolds and a genome size of 69.7 Mb. The expanded genome size in P. subalpina was not due to the proliferation of transposable elements or other repeats, as is the case with other ascomycetous genomes. Instead, P. subalpina revealed an expanded gene inventory that includes 20,173 gene models. Comparative genome analysis of P. subalpina with 13 ascomycetes shows that P. subalpina uses a versatile gene inventory including genes specific for pathogens and saprophytes. Moreover, the gene inventory for carbohydrate active enzymes (CAZymes) was expanded including genes involved in degradation of biopolymers, such as pectin, hemicellulose, cellulose and lignin.ConclusionsThe analysis of a globally distributed root endophyte allowed detailed insights in the gene inventory and genome organization of a yet largely neglected group of organisms. We showed that the ubiquitous root endophyte P. subalpina has a broad gene inventory that links pathogenic and saprophytic lifestyles.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3369-8) contains supplementary material, which is available to authorized users.

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A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

Cited by 33 publications

References 57 publications

Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse

Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse

Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis

Globally distributed root endophyte Phialocephala subalpina links pathogenic and saprophytic lifestyles

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