Isolation of a Novel Cyclic Hexadepsipeptide Pipalamycin from Streptomyces as an Apoptosis-inducing Agent.

Uchihata, Yuki; Ando, Noritaka; Ikeda, Yoko; Kondo, Shinichi; Hamada, Masa; Umezawa, Kazuo

doi:10.7164/antibiotics.55.1

Cited by 49 publications

(12 citation statements)

References 7 publications

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“…Structurally-related natural products, in the past decades, have been continuously discovered from Actinomycetes including A83586C [ 2 ], azinothricin [ 3 ], citropeptin [ 4 ], diperamycin [ 5 ], kettapeptin [ 6 ], IC101 [ 7 ], L-156,602 [ 8 ], pipalamycin [ 9 ], polyoxypeptin [ 10 ] and variapeptin [ 11 ] (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the aurantimycin biosynthetic gene cluster and enhancing its production by manipulating two pathway-specific activators in Streptomyces aurantiacus JA 4570

et al. 2016

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BackgroundAurantimycin (ATM), produced by Streptomyces aurantiacus JA 4570, is a potent antimicrobial and antitumor antibiotic. Although the chemical structure of ATM is highly distinctive and features a cyclohexadepsipeptide scaffold attached with a C14 acyl side chain, little is known about its biosynthetic pathway and regulatory mechanism.ResultsIn this work, we report the identification and characterization of the ATM biosynthetic gene cluster from S. aurantiacus JA 4570. Targeted inactivation of artG, coding for a NRPS enzyme, completely abolished ATM production, thereof demonstrating the target gene cluster (art) is responsible for ATM biosynthesis. Moreover, four NRPS adenylation (A) domains including a freestanding enzyme ArtC have been characterized in vitro, whose substrate specificities are consistent with in silico analysis. Further genetic analysis of the two regulatory genes artB and artX unambiguously suggested both of them play positive roles in ATM biosynthesis, and ATM-A production was thus rationally enhanced to about 2.5 fold via tandem overexpression of artB and artX in S. aurantiacus JA 4570.ConclusionsThese results will provide the basis for the understanding of precise mechanisms for ATM biosynthesis, and open the way for both rational construction of high-production ATM producer and orient-directed generation of designer ATM derivatives via synthetic biology strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0559-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Characterization of the aurantimycin biosynthetic gene cluster and enhancing its production by manipulating two pathway-specific activators in Streptomyces aurantiacus JA 4570

et al. 2016

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“…Other PA-containing cyclic hexapeptides contain only three PA moieties, as, for example, the svetamycins (Dardic et al 2017) or NW-G10 and NW-G11 (Wei et al 2012), two PA moieties, as, for example, depsidomycin (Isshiki et al 1990), piperastatin A þ B Murakami, Harada, Yamazaki et al 1996) or pipalamcin (Uchihata et al 2002), or only one PA moiety as in the case for marformycins (Liu et al 2015).…”

Section: Piperazic Acid Containing Peptidesmentioning

confidence: 99%

Piperazic acid containing peptides produced by an endophytic Streptomyces sp. isolated from the medicinal plant Atropa belladonna

Bekiesch

Oberhofer

Sykora

et al. 2019

Natural Product Research

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The culture broth of endophytic Streptomyces sp. AB100, isolated from the shoots of medicinal plant Atropa belladonna (L.) was investigated for the presence of antibacterial compounds. After initial testing followed by bioactivity-guided fractionation, six new piperazic acid (PA)-containing congeners of two known peptides, JBIR-39 and JBIR-40, were identified by HR-MS/MS and NMR analyses. Only the dehydroxylated hexapeptidic derivatives with unusual incorporation of four PA moieties exhibited weak antibacterial activity against Gram-positive test organism Bacillus subtilis. A 16S rDNA-based phylogenetic tree of known Streptomyces spp. producing PA-containing hexapeptides isolated from different habitats and endophyte Streptomyces AB100 showed considerable diversity, suggesting that these metabolites may play an important environmental role beyond their antibacterial activity.

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“…Pipalamycin induced apoptosis in apoptosis-resistant human pancreatic adenocarcinoma AsPC-1 cells. It also showed antibacterial activity on Gram-positive bacteria, such as Staphylococcus aureus and Micrococcus luteus (Uchihata et al, 2002).…”

Section: Epoxy-and Pyrane-containing Fatty Acidsmentioning

confidence: 99%

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

Dembitsky¹

2017

Int. J. Curr. Res. Biosci. Plant Biol.

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A b s t r a c t A r t i c l e I n f oThis review is a comprehensive survey of unique, unusual, and rare fatty acids incorporated into natural marine and terrestrial peptides obtained from fungi, fungal endophytes, lichenized ascomycetes, basidiomycetes, and actinomycetes. Lots of fungal peptides display important biological activities of interest, which includes antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, immunosuppressive properties, and other pharmacological activities. There is no doubt that they are of great importance, especially in medicinal chemistry and/or pharmaceutical application. This review presents structures of more than 150 fatty acids, incorporated into marine and terrestrial fungal lipopeptides.

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Isolation of a Novel Cyclic Hexadepsipeptide Pipalamycin from Streptomyces as an Apoptosis-inducing Agent.

Cited by 49 publications

References 7 publications

Characterization of the aurantimycin biosynthetic gene cluster and enhancing its production by manipulating two pathway-specific activators in Streptomyces aurantiacus JA 4570

Characterization of the aurantimycin biosynthetic gene cluster and enhancing its production by manipulating two pathway-specific activators in Streptomyces aurantiacus JA 4570

Piperazic acid containing peptides produced by an endophytic Streptomyces sp. isolated from the medicinal plant Atropa belladonna

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

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