Extraribosomal cyclic tetradepsipeptides beauverolides: profiling and modeling the fragmentation pathways

Jegorov, Alexandr; Paizs, Béla; Kuzma, Marek; Zabka, Martin; Landa, Z.; Šulc, Miroslav; Barrow, Mark P.; Havlı́ček, Vladimı́r

doi:10.1002/jms.674

Cited by 29 publications

(32 citation statements)

References 56 publications

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“…are cyclic tetradepsipeptides containing C 9 - or C 11 -β-hydroxy acid residues [32] (Figure 4a). More than twenty different beauverolides have been identified, and sequencing of beauverolides by tandem mass spectrometry has been well described [32], [33]. The product ion mass spectra we obtained in this study were virtually identical to those in the literature.…”

Section: Resultssupporting

confidence: 73%

Metabolomics Reveals the Heterogeneous Secretome of Two Entomopathogenic Fungi to Ex Vivo Cultured Insect Tissues

et al. 2013

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Fungal entomopathogens rely on cellular heterogeneity during the different stages of insect host infection. Their pathogenicity is exhibited through the secretion of secondary metabolites, which implies that the infection life history of this group of environmentally important fungi can be revealed using metabolomics. Here metabolomic analysis in combination with ex vivo insect tissue culturing shows that two generalist isolates of the genus Metarhizium and Beauveria, commonly used as biological pesticides, employ significantly different arrays of secondary metabolites during infectious and saprophytic growth. It also reveals that both fungi exhibit tissue specific strategies by a distinguishable metabolite secretion on the insect tissues tested in this study. In addition to showing the important heterogeneous nature of these two entomopathogens, this study also resulted in the discovery of several novel destruxins and beauverolides that have not been described before, most likely because previous surveys did not use insect tissues as a culturing system. While Beauveria secreted these cyclic depsipeptides when encountering live insect tissues, Metarhizium employed them primarily on dead tissue. This implies that, while these fungi employ comparable strategies when it comes to entomopathogenesis, there are most certainly significant differences at the molecular level that deserve to be studied.

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Section: Resultssupporting

confidence: 73%

Metabolomics Reveals the Heterogeneous Secretome of Two Entomopathogenic Fungi to Ex Vivo Cultured Insect Tissues

et al. 2013

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“…However, many non-ribosomal cyclic peptides are cyclized via lactone formation and include nonstandard amino acids 53. Theoretical calculations suggested that cyclic peptides favor lactone bond as the initial ring opening site and also the fragmentation pathway of cyclic peptides differs when lactone bond(s) were involved 29. It is therefore important to establish how these other structural features impact the fragmentation data and the results analyzed by the MS-CPA program.…”

Section: Results and Disscussionmentioning

confidence: 99%

Interpretation of Tandem Mass Spectra Obtained from Cyclic Nonribosomal Peptides

Liu

Meluzzi

et al. 2009

Anal. Chem.

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Natural and non-natural cyclic peptides are a crucial component in drug discovery programs because of their considerable pharmaceutical properties. Cyclosporin, microcystins and nodularins all are notable pharmacologically important cyclic peptides. Because these biologically active peptides are often biosynthesized non-ribosomally, they often contain non-standard amino acids, thus increasing the complexity of the resulting tandem mass spectrometry data. In addition, due to the cyclic nature, the fragmentation patterns of many of these peptides showed much higher complexity when compared to related counterparts. Therefore, at the present time it is still difficult to annotate cyclic peptides MS/MS spectra. In this current work, an annotation program was developed for the annotation and characterization of tandem mass spectra obtained from cyclic peptides. This program, which we call MS-CPA is available as a web tool (http://lol.ucsd.edu/ms-cpa_v1/Input.py). Using this program, we have successfully annotated the sequence of representative cyclic peptides, such as seglitide, tyrothricin, desmethoxymajusculamide C, dudawalamide A and cyclomarins in a rapid manner, and also were able to provide the first-pass structure evidence of a newly discovered natural product base on predicted sequence. This compound is not available in sufficient quantities for structural elucidation by other means such as NMR.1 In addition to the development of this cyclic annotation program, it was observed that some cyclic peptides fragmented in unexpected ways resulting in the scrambling of sequences. In sum, MS-CPA not only provides a platform for rapid confirmation and annotation of tandem mass spectrometry data obtained with cyclic peptides but also enables quantitative analysis of the ion intensities. This program facilitates cyclic peptide analysis, sequencing, but also acts as a useful tool to investigate the uncommon fragmentation phenomena of cyclic peptides and aids the characterization of newly discovered cyclic peptides encountered in drug discovery programs.

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“…Loss of H 2 O or NH 3 is a common phenomenon found for cyclic peptides, even if no hydroxyl groups are present in the molecule [40], [44], [46], [48], [60]–[64]. Loss of H 2 O and NH 3 at the same time is possible, and also side chain neutral losses in conjunction with H 2 O or NH 3 losses have been observed [27], [45], [47].…”

Section: Methodsmentioning

confidence: 99%

mMass as a Software Tool for the Annotation of Cyclic Peptide Tandem Mass Spectra

2012

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Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and the complex fragmentation patterns observed. Even though several software tools for cyclic peptide tandem mass spectra annotation have been published, these tools are still unable to annotate a majority of the signals observed in experimentally obtained mass spectra. They are thus not suitable for extensive mass spectrometric characterization of these compounds. This lack of advanced and user-friendly software tools has motivated us to extend the fragmentation module of a freely available open-source software, mMass (http://www.mmass.org), to allow for cyclic peptide tandem mass spectra annotation and interpretation. The resulting software has been tested on several cyanobacterial and other naturally occurring peptides. It has been found to be superior to other currently available tools concerning both usability and annotation extensiveness. Thus it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides.

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Extraribosomal cyclic tetradepsipeptides beauverolides: profiling and modeling the fragmentation pathways

Cited by 29 publications

References 56 publications

Metabolomics Reveals the Heterogeneous Secretome of Two Entomopathogenic Fungi to Ex Vivo Cultured Insect Tissues

Metabolomics Reveals the Heterogeneous Secretome of Two Entomopathogenic Fungi to Ex Vivo Cultured Insect Tissues

Interpretation of Tandem Mass Spectra Obtained from Cyclic Nonribosomal Peptides

mMass as a Software Tool for the Annotation of Cyclic Peptide Tandem Mass Spectra

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