Xenortide Biosynthesis by Entomopathogenic <i>Xenorhabdus nematophila</i>

Reimer, Daniela; Nollmann, Friederike I.; Schultz, Katharina; Kaiser, Marcel; Bode, Helge B.

doi:10.1021/np500390b

Cited by 43 publications

(36 citation statements)

References 34 publications

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“…Xenocoumacins, xenematides, and xenortides display antimicrobial activity against a broad spectrum of bacteria ( Lang et al, 2008 ) and are thought to eliminate microbial competitors to defend the nutrients within the insect cadaver. Xenematides have insecticidal activity, rhabdopeptides are active against insect hemocytes ( Lang et al, 2008 ; Reimer et al, 2013 ), and xenortides are cytotoxic against mammalian L6 cells ( Reimer et al, 2014 ). The regulation of these compounds by Lrp is in agreement with the previously reported finding that this regulator is needed for virulence ( Cowles et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

The Global Regulators Lrp, LeuO, and HexA Control Secondary Metabolism in Entomopathogenic Bacteria

Engel

Windhorst

et al. 2017

Front. Microbiol.

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Photorhabdus luminescens TTO1 and Xenorhabdus nematophila HGB081 are insect pathogenic bacteria and producers of various structurally diverse bioactive natural products. In these entomopathogenic bacteria we investigated the role of the global regulators Lrp, LeuO, and HexA in the production of natural products. Lrp is a general activator of natural product biosynthesis in X. nematophila and for most compounds in TTO1. Microarray analysis confirmed these results in X. nematophila and enabled the identification of additional biosynthesis gene clusters (BGC) regulated by Lrp. Moreover, when promoters of two X. nematophila BGC were analyzed, transcriptional activation by Lrp was observed. In contrast, LeuO in X. nematophila and P. luminescens has both repressing and activating features, depending on the natural product examined. Furthermore, heterologous overexpression of leuO from X. nematophila in the closely related Xenorhabdus szentirmaii resulted in overproduction of several natural products including novel compounds. The presented findings could be of importance for establishing a tool for overproduction of secondary metabolites and subsequent identification of novel compounds.

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Section: Discussionmentioning

confidence: 99%

The Global Regulators Lrp, LeuO, and HexA Control Secondary Metabolism in Entomopathogenic Bacteria

Engel

Windhorst

et al. 2017

Front. Microbiol.

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“…8C). Furthermore, when Pb62A was used as a starting module in XndB involved in xenortide biosynthesis, 135 nevaltophins with phenylalanine motif 26h-i were produced. 131 The results provided a platform for engineered biosynthesis further expanding the nematophin chemical space.…”

Section: Nonribosomal Peptidesmentioning

confidence: 99%

Bacterial pathogens: threat or treat (a review on bioactive natural products from bacterial pathogens)

Maglangit

Deng

2021

Nat. Prod. Rep.

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“…A related group of linear peptides, xenortides A–D (xenortide A is shown, Fig. ), and their associated two‐module NRPS gene cluster ( xndAB ) have been identified in X. nematophila , with xenortides C and D representing analogs of A and B, respectively, that incorporate N ‐methyl‐ l ‐valine in the place of N ‐methyl‐ l ‐leucine . Linear peptides with broad‐spectrum antimicrobial activities, for example, bicornutin A (Fig.…”

Section: Peptide Metabolitesmentioning

confidence: 99%

Bioactive natural products from novel microbial sources

Challinor

Bode

2015

Annals of the New York Academy of Sciences

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106

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Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics.

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Xenortide Biosynthesis by Entomopathogenic Xenorhabdus nematophila

Cited by 43 publications

References 34 publications

The Global Regulators Lrp, LeuO, and HexA Control Secondary Metabolism in Entomopathogenic Bacteria

The Global Regulators Lrp, LeuO, and HexA Control Secondary Metabolism in Entomopathogenic Bacteria

Bacterial pathogens: threat or treat (a review on bioactive natural products from bacterial pathogens)

Bioactive natural products from novel microbial sources

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