Cyclopeptide toxins of lethal amanitas: Compositions, distribution and phylogenetic implication

Tang, Shanshan; Zhou, Qian; He, Zhengmi; Luo, Tao; Zhang, Ping; Cai, Qing; Yang, Zhu‐Liang; Chen, Jia; Chen, Zuohong

doi:10.1016/j.toxicon.2016.07.018

Cited by 41 publications

(43 citation statements)

References 47 publications

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“…MSDIN genes encoding amatoxin and phallotoxin were discovered in 2007 [5], but there has been no related evidence of MSDIN genes encoding virotoxins to date. It has been reported that A. subpallidorosea and A. virosa contain virotoxins [3,26]. In this study, toxin genes of the two lethal Amanita species were also identified, and no virotoxin genes were found.…”

Section: Discussionmentioning

confidence: 72%

Diversity of MSDIN family members in amanitin-producing mushrooms and the phylogeny of the MSDIN and prolyl oligopeptidase genes

Long

Fang

et al. 2020

Preprint

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Background Amanitin-producing mushrooms, mainly distributed in the genera Amanita , Galerina and Lepiota , possess MSDIN gene family for the biosynthesis of many cyclopeptides catalyzed by prolyl oligopeptidase (POP). Recently, transcriptome sequencing has proven to be a efficient way to mine MSDIN and POP genes in these lethal mushrooms. Until now, only A . palloides and A. bisporigera from North America and A . exitialis from Asia have been studied based on transcriptome analysis. However, MSDIN and POP genes of many amanitin-producing mushrooms in China remain unstudied, and hence the transcriptomes of these speices deserve to be analysed. Results In this study, the MSDIN and POP genes from ten Amanita species, two Galerina species and Lepiota venenata were studied and the phylogenetic relationships of their MSDIN and POP genes were analyzed. Through transcriptome sequencing and PCR cloning, 19 POP genes and 151 MSDIN genes predicted to encode 98 non-duplicated cyclopeptides, including α-amanitin, β-amanitin, phallacidin, phalloidin and 94 unknown peptides, were found in these species. Phylogenetic analysis showed that toxin peptide genes were clustered depending on the chemical substance within genus while depending on the taxonomy between genus and that the POPA genes of Amanita , Galerina and Lepiota were clustered and separated in three different groups, but the POPB genes of the three distinct genera were clustered in a highly monophyletic group. Conclusions These results above indicate that lethal Amanita species have the genetic capacity to produce numerous cyclopeptides, most of which are unknown, while lethal Galerina and Lepiota species seem to only have the genetic capacity to produce α-amanitin. Additionally, the POPB phylogeny of Amanita , Galerina and Lepiota conflicts with the taxonomic status of the three genera, suggesting that horizontal gene transfer might occur among the three genera.

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Section: Discussionmentioning

confidence: 72%

Diversity of MSDIN family members in amanitin-producing mushrooms and the phylogeny of the MSDIN and prolyl oligopeptidase genes

Long

Fang

et al. 2020

Preprint

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“…Most fungal RiPPs have therefore been characterized through a top-down approach, leading to the identification of the amatoxins [37], phallotoxins [37], virotoxins (all reviewed in [38]), and more recently the epichloëcyclins [39], the ustiloxins [40], and the phomopsins [41]. Increasing knowledge of the biosynthetic enzymes associated with fungal RiPPs has revealed that the ustiloxins and phomopsins are widespread in the dikarya subkingdom [41,42].…”

Section: Examples Of Bottom-up Ripp Discoverymentioning

confidence: 99%

Ribosomally synthesized and post-translationally modified peptide natural product discovery in the genomic era

Hetrick

Donk

2017

Current Opinion in Chemical Biology

124

105

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In the past 15 years, the cost of sequencing a genome has plummeted. Consequently, the number of sequenced bacterial genomes has exponentially increased, and methods for natural product discovery have evolved rapidly to take advantage of the wealth of genomic data. This review highlights applications of genome mining software to compare and organize large-scale data sets and methods for identifying unique biosynthetic pathways amongst the thousands of ribosomally synthesized and post-translationally modified peptide (RiPP) gene clusters. We also discuss a small number of the many RiPPs discovered in the years 2014–2016.

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“…Suggested by HPLC analyses in many laboratories, the most significant peptide production in Amanita species is attributed to the major toxins, i.e., α-amanita, β-amanitin, phallacidin and phalloidin [13,20,21]. Noticeably, a number of less significant peaks were present in the vicinity of these known peptides, many of which are of insufficient amount for further analyses via conventional methods.…”

Section: Introductionmentioning

confidence: 99%

Novel cyclic peptides from lethal Amanita species through a genomic approach, and major peptide toxins in the ectomycorrhizal association

Luo¹,

Zhou²,

Li³

et al. 2020

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Background: Most species in the genus Amanita are ectomycorrhizal fungi, and the cyclic peptide toxins that some species produce are notoriously deadly. In total, around 25 of these peptides were found in the fruiting bodies over the past 82 years, and whether any of them are present in the mycorrhizae is unknown. Reportedly, sequenced lethal Amanita genomes harbor a significant number of precursor genes of MSDIN family, indicating there could be a much larger capacity for cyclic peptide production in these mushrooms. However, it is largely unknown that to what extent these genes are transcribed, and further, translated into true cyclic peptides. Method:In this study, three poisonous Amanita species, A. rimosa, A. exitialis and A. subjunquillea, were sequenced through PacBio and Illumina techniques. For expression analysis, one strain of A.subjunquillea was sequenced through RNA-Seq. A genome-guided approach was adopted to identify cyclic peptides by coupling predicted toxin-biosynthetic genes with mass spectrometry (MS and MS/MS). To investigate whether any of the toxins were express in the microbiome, profiling of known major toxins was conducted on A. subjunquillea mycorrhizae via HRMS and gene cloning. Results:The resultant genomes showed significant potential to produce known and unknown cyclic peptides. Together with our 2 previously sequenced genomes, in total 37 unknown MSDIN genes were discovered. Expression of over 90% of the MSDIN genes was demonstrated in two strains of A. subjunquillea. Through the genome-guided approach, 12 MSDIN genes were found to produce true, novel cyclic peptides with no additional posttranslational modifications. When the ectomycorrhizae of A. subjunquillea were analyzed by MS, all major toxins were detected. The corresponding MSDINs for these cyclic peptides were successfully cloned directly from the mycorrhizae. Conclusions:The genome-guided approach provided a speedy method to identify cyclic peptides both in Amanita mushrooms and in the ectomycorrhizae. In this study, a significant number of novel MSDIN genes were discovered, most of which were found to be expressed in the tested species. The identification of the 12 novel cyclic peptides strongly suggests that Amanita species possess a much larger reservoir of these peptides than previously thought. This is the first report to demonstrate that the cyclic peptides in Amanita species are expressed in the mycorrhizal association. All four major

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Cyclopeptide toxins of lethal amanitas: Compositions, distribution and phylogenetic implication

Cited by 41 publications

References 47 publications

Diversity of MSDIN family members in amanitin-producing mushrooms and the phylogeny of the MSDIN and prolyl oligopeptidase genes

Diversity of MSDIN family members in amanitin-producing mushrooms and the phylogeny of the MSDIN and prolyl oligopeptidase genes

Ribosomally synthesized and post-translationally modified peptide natural product discovery in the genomic era

Novel cyclic peptides from lethal Amanita species through a genomic approach, and major peptide toxins in the ectomycorrhizal association

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