Phototemtide A, a Cyclic Lipopeptide Heterologously Expressed from <i>Photorhabdus temperata</i> Meg1, Shows Selective Antiprotozoal Activity

Zhao, Lei; Vo, Tien Duy; Kaiser, Marcel; Bode, Helge B.

doi:10.1002/cbic.201900665

Cited by 13 publications

(16 citation statements)

References 41 publications

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“…Lipopeptides are a diverse class of molecules containing a nonpolar fatty acid chain and amino acid residues of varying length and hydrophobicity. Many bacterial lipopeptides originate from NRPSs. , These amphiphilic molecules display a variety of bioactivities from antimicrobial, to surfactant, to cell signaling . Most antimicrobial lipopeptides are macrocyclic; however, there are also several reports of linear lipopeptides with bioactivities such as paenipeptin (antibacterial) and holrhizin A (surfactant) .…”

Section: Resultsmentioning

confidence: 99%

A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides

Cho

Hamchand

et al. 2021

J. Nat. Prod.

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The entomopathogenic bacterium Xenorhabdus bovienii exists in a mutualistic relationship with nematodes of the genus Steinernema. Free-living infective juveniles of Steinernema prey on insect larvae and regurgitate X. bovienii within the hemocoel of a host larva. X. bovienii subsequently produces a complex array of specialized metabolites and effector proteins that kill the insect and regulate various aspects of the trilateral symbiosis. While Xenorhabdus species are rich producers of secondary metabolites, many of their biosynthetic gene clusters remain uncharacterized. Here, we describe a nonribosomal peptide synthetase (NRPS) identified through comparative genomics analysis that is widely conserved in Xenorhabdus species. Heterologous expression of this NRPS gene from X. bovienii in E. coli led to the discovery of a family of lipo-tripeptides that chromatographically appear as pairs, containing either a C-terminal carboxylic acid or carboxamide. Coexpression of the NRPS with the leupeptin protease inhibitor pathway enhanced production, facilitating isolation and characterization efforts. The new lipo-tripeptides were also detected in wild-type X. bovienii cultures. These metabolites, termed bovienimides, share an uncommon C-terminal d-citrulline residue. The NRPS lacked a dedicated chain termination domain, resulting in product diversification and release from the assembly line through reactions with ammonia, water, or exogenous alcohols.

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Section: Resultsmentioning

confidence: 99%

A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides

Cho

Hamchand

et al. 2021

J. Nat. Prod.

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“…To defend this from colonization by microbial competitors, a broad spectrum of antimicrobials is produced. These include antifungals: biocornutin ( Böszörményi et al, 2009 ), cabanillasin ( Houard et al, 2013 ), EP-19, GP-20 ( Xiao et al, 2012 ), and xenocoumacin ( Yang et al, 2011 ); antibacterials: darobactin ( Imai et al, 2019 ), xenematide ( Lang et al, 2008 ), photoditritide ( Zhao et al, 2019 ), xenobactin ( Grundmann et al, 2013 ), odilorhabdins ( Pantel et al, 2018 ), xenorhabdin ( McInerney et al, 1991 ), and PAX peptides ( Gualtieri et al, 2009 ); antiprotozoals: phototemtide ( Zhao et al, 2020 ), szentiamide ( Ohlendorf et al, 2011 ), chaiyaphumins ( Grundmann et al, 2014 ), rhabdopeptide/xenortide-like peptides (RXP) ( Zhao L. et al, 2018 ), xenortide ( Reimer et al, 2014 ), xenoamicin ( Zhou et al, 2013 ), and ambactin ( Schimming et al, 2014 ); and cytotoxic agents: fabclavines ( Wenski et al, 2020 ) and phenylethylamine (PEA) derivatives ( Proschak et al, 2011 ).…”

Section: The Nematode-bacterium Lifecycle and Bacterial Biomoleculesmentioning

confidence: 99%

Nematophilic bacteria associated with entomopathogenic nematodes and drug development of their biomolecules

Awori

2022

Front. Microbiol.

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The importance of Xenorhabdus and Photorhabdus symbionts to their respective Steinernema and Heterorhabditis nematode hosts is that they not only contribute to their entomopathogenicity but also to their fecundity through the production of small molecules. Thus, this mini-review gives a brief introductory overview of these nematophilic bacteria. Specifically, their type species, nematode hosts, and geographic region of isolations are tabulated. The use of nucleotide sequence-based techniques for their species delineation and how pangenomes can improve this are highlighted. Using the Steinernema–Xenorhabdus association as an example, the bacterium-nematode lifecycle is visualized with an emphasis on the role of bacterial biomolecules. Those currently in drug development are discussed, and two potential antimalarial lead compounds are highlighted. Thus, this mini-review tabulates forty-eight significant nematophilic bacteria and visualizes the ecological importance of their biomolecules. It further discusses three of these biomolecules that are currently in drug development. Through it, one is introduced to Xenorhabdus and Photorhabdus bacteria, their natural production of biomolecules in the nematode-bacterium lifecycle, and how these molecules are useful in developing novel therapies.

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“…This new cyclic lipopeptide has three more minor derivatives. It has been reported that this peptide has weak antiprotozoal activity with IC 50 = 9.8 μM, against deadly plasmodium species Plasmodium falciparum ( Zhao et al, 2020 ). New peptide drugs have gained attention due to their easy synthesis, low toxicity, fewer side effects, and rapid elimination ( Du et al, 2015 ).…”

Section: Photorhabdus As Source Of Antiprotozoal Compoundsmentioning

confidence: 99%

Heterorhabditis and Photorhabdus Symbiosis: A Natural Mine of Bioactive Compounds

et al. 2022

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Phylum Nematoda is of great economic importance. It has been a focused area for various research activities in distinct domains across the globe. Among nematodes, there is a group called entomopathogenic nematodes, which has two families that live in symbiotic association with bacteria of genus Xenorhabdus and Photorhabdus, respectively. With the passing years, researchers have isolated a wide array of bioactive compounds from these symbiotically associated nematodes. In this article, we are encapsulating bioactive compounds isolated from members of the family Heterorhabditidae inhabiting Photorhabdus in its gut. Isolated bioactive compounds have shown a wide range of biological activity against deadly pathogens to both plants as well as animals. Some compounds exhibit lethal effects against fungi, bacteria, protozoan, insects, cancerous cell lines, neuroinflammation, etc., with great potency. The main aim of this article is to collect and analyze the importance of nematode and its associated bacteria, isolated secondary metabolites, and their biomedical potential, which can serve as potential leads for further drug discovery.

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Phototemtide A, a Cyclic Lipopeptide Heterologously Expressed from Photorhabdus temperata Meg1, Shows Selective Antiprotozoal Activity

Cited by 13 publications

References 41 publications

A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides

A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides

Nematophilic bacteria associated with entomopathogenic nematodes and drug development of their biomolecules

Heterorhabditis and Photorhabdus Symbiosis: A Natural Mine of Bioactive Compounds

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