Rhabdopeptide/Xenortide-like Peptides from <i>Xenorhabdus innexi</i> with Terminal Amines Showing Potent Antiprotozoal Activity

Zhao, Lei; Kaiser, Marcel; Bode, Helge B.

doi:10.1021/acs.orglett.8b01975

Cited by 24 publications

(35 citation statements)

References 12 publications

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“…As an example, X. indica and X. cabanillasii showed an additional bioactivity against Gram-negative bacteria even without fabclavine production (Table 3). This bioactivity might be caused by other compound(s) as both strains have the potential to produce further bioactive SMs, such as cabanillasin, PAX peptides, or rhabdopeptides [26,[44][45][46], which will be studied in the future. Furthermore, the identification of fabclavine derivatives described here might support recent studies that revealed Xenorhabdus and Photorhabdus strains having ascaricidal or larvicidal activity.…”

Section: Resultsmentioning

confidence: 99%

Fabclavine diversity in Xenorhabdus bacteria

Wenski

Çimen

Berghaus

et al. 2020

Beilstein J. Org. Chem.

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The global threat of multiresistant pathogens has to be answered by the development of novel antibiotics. Established antibiotic applications are often based on so-called secondary or specialized metabolites (SMs), identified in large screening approaches. To continue this successful strategy, new sources for bioactive compounds are required, such as the bacterial genera Xenorhabdus or Photorhabdus. In these strains, fabclavines are widely distributed SMs with a broad-spectrum bioactivity. Fabclavines are hybrid SMs derived from nonribosomal peptide synthetases (NRPS), polyunsaturated fatty acid (PUFA), and polyketide synthases (PKS). Selected Xenorhabdus and Photorhabdus mutant strains were generated applying a chemically inducible promoter in front of the suggested fabclavine (fcl) biosynthesis gene cluster (BGC), followed by the analysis of the occurring fabclavines. Subsequently, known and unknown derivatives were identified and confirmed by MALDI–MS and MALDI–MS2 experiments in combination with an optimized sample preparation. This led to a total number of 22 novel fabclavine derivatives in eight strains, increasing the overall number of fabclavines to 32. Together with the identification of fabclavines as major antibiotics in several entomopathogenic strains, our work lays the foundation for the rapid fabclavine identification and dereplication as the basis for future work of this widespread and bioactive SM class.

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Section: Resultsmentioning

confidence: 99%

Fabclavine diversity in Xenorhabdus bacteria

Wenski

Çimen

Berghaus

et al. 2020

Beilstein J. Org. Chem.

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“…Annotations included Mass2Motifs that form peptidic substructures related to well-known Xenorhabdus peptidic families such as the commonly found bioactive rhabdopeptides and the related xenortides [52,53]. We could annotate two rhabdopeptide-related motifs with frequencies of 231 and 186 (3.7% and 3.0% of nodes, respectively).…”

Section: Resultsmentioning

confidence: 99%

MolNetEnhancer: Enhanced Molecular Networks by Integrating Metabolome Mining and Annotation Tools

et al. 2019

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Metabolomics has started to embrace computational approaches for chemical interpretation of large data sets. Yet, metabolite annotation remains a key challenge. Recently, molecular networking and MS2LDA emerged as molecular mining tools that find molecular families and substructures in mass spectrometry fragmentation data. Moreover, in silico annotation tools obtain and rank candidate molecules for fragmentation spectra. Ideally, all structural information obtained and inferred from these computational tools could be combined to increase the resulting chemical insight one can obtain from a data set. However, integration is currently hampered as each tool has its own output format and efficient matching of data across these tools is lacking. Here, we introduce MolNetEnhancer, a workflow that combines the outputs from molecular networking, MS2LDA, in silico annotation tools (such as Network Annotation Propagation or DEREPLICATOR), and the automated chemical classification through ClassyFire to provide a more comprehensive chemical overview of metabolomics data whilst at the same time illuminating structural details for each fragmentation spectrum. We present examples from four plant and bacterial case studies and show how MolNetEnhancer enables the chemical annotation, visualization, and discovery of the subtle substructural diversity within molecular families. We conclude that MolNetEnhancer is a useful tool that greatly assists the metabolomics researcher in deciphering the metabolome through combination of multiple independent in silico pipelines.

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“…While xenortides were originally discovered in X. nematophyla [ 126 ] rhabdopeptides are widespread in both Xenorhabdus and Photorhabdus strains, in the latter mostly represented by the mevalagmapeptides ( Figure 5 ) [ 120 , 133 , 134 ]. Rhabdopeptides are linear molecules containing two to seven amino acid residues, mainly valine, phenylalanine and leucine (often N-methylated) fused to a terminal amine, which is variable in structure and usually depends on the pool of available amines in each producer strain [ 134 , 135 ]. Interestingly, these molecules are synthesized by NRPS systems consisting of just two to three modules encoded in stand-alone proteins.…”

Section: Entomopathogenic Bacteriamentioning

confidence: 99%

Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

Santos‐Aberturas

Vior

2022

Antibiotics

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Bacterial secondary metabolites represent an invaluable source of bioactive molecules for the pharmaceutical and agrochemical industries. Although screening campaigns for the discovery of new compounds have traditionally been strongly biased towards the study of soil-dwelling Actinobacteria, the current antibiotic resistance and discovery crisis has brought a considerable amount of attention to the study of previously neglected bacterial sources of secondary metabolites. The development and application of new screening, sequencing, genetic manipulation, cultivation and bioinformatic techniques have revealed several other groups of bacteria as producers of striking chemical novelty. Biosynthetic machineries evolved from independent taxonomic origins and under completely different ecological requirements and selective pressures are responsible for these structural innovations. In this review, we summarize the most important discoveries related to secondary metabolites from alternative bacterial sources, trying to provide the reader with a broad perspective on how technical novelties have facilitated the access to the bacterial metabolic dark matter.

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Rhabdopeptide/Xenortide-like Peptides from Xenorhabdus innexi with Terminal Amines Showing Potent Antiprotozoal Activity

Cited by 24 publications

References 12 publications

Fabclavine diversity in Xenorhabdus bacteria

Fabclavine diversity in Xenorhabdus bacteria

MolNetEnhancer: Enhanced Molecular Networks by Integrating Metabolome Mining and Annotation Tools

Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

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