Dataset Information

Bistratamides M and N, Oxazole-Thiazole Containing Cyclic Hexapeptides Isolated from Lissoclinum bistratum Interaction of Zinc (II) with Bistratamide K.

ABSTRACT: Two novel oxazole-thiazole containing cyclic hexapeptides, bistratamides M (1) and N (2) have been isolated from the marine ascidian Lissoclinum bistratum (L. bistratum) collected in Raja Ampat (Papua Bar, Indonesia). The planar structure of 1 and 2 was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of the Marfey's and advanced Marfey's methods after ozonolysis followed by acid-catalyzed hydrolysis. The interaction between zinc (II) and the naturally known bistratamide K (3), a cyclic hexapeptide isolated from a different specimen of Lissoclinum bistratum, was monitored by ¹H and ¹³C NMR. The results obtained are consistent with the proposal that these peptides are biosynthesized for binding to metal ions. Compounds 1 and 2 display moderate cytotoxicity against four human tumor cell lines with GI₅₀ values in the micromolar range.

SUBMITTER: Urda C

PROVIDER: S-EPMC5532651 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Bistratamides M and N, Oxazole-Thiazole Containing Cyclic Hexapeptides Isolated from Lissoclinum bistratum Interaction of Zinc (II) with Bistratamide K.

Urda Carlos C Fernández Rogelio R Rodríguez Jaime J Pérez Marta M Jiménez Carlos C Cuevas Carmen C

Marine drugs 20170701 7

Two novel oxazole-thiazole containing cyclic hexapeptides, bistratamides M (1) and N (2) have been isolated from the marine ascidian Lissoclinum bistratum (L. bistratum) collected in Raja Ampat (Papua Bar, Indonesia). The planar structure of 1 and 2 was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of the Marfey ...[more]

PMID: 28671564

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Project description:BACKGROUND:Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a burgeoning class of natural products with diverse activity that share a similar origin and common features in their biosynthetic pathways. The precursor peptides of these natural products are ribosomally produced, upon which a combination of modification enzymes installs diverse functional groups. This genetically encoded peptide-based strategy allows for rapid diversification of these natural products by mutation in the precursor genes merged with unique combinations of modification enzymes. Thiazole/oxazole-modified microcins (TOMMs) are a class of RiPPs defined by the presence of heterocycles derived from cysteine, serine, and threonine residues in the precursor peptide. TOMMs encompass a number of different families, including but not limited to the linear azol(in)e-containing peptides (streptolysin S, microcin B17, and plantazolicin), cyanobactins, thiopeptides, and bottromycins. Although many TOMMs have been explored, the increased availability of genome sequences has illuminated several unexplored TOMM producers. METHODS:All YcaO domain-containing proteins (D protein) and the surrounding genomic regions were were obtained from the European Molecular Biology Laboratory (EMBL) and the European Bioinformatics Institute (EBI). MultiGeneBlast was used to group gene clusters contain a D protein. A number of techniques were used to identify TOMM biosynthetic gene clusters from the D protein containing gene clusters. Precursor peptides from these gene clusters were also identified. Both sequence similarity and phylogenetic analysis were used to classify the 20 diverse TOMM clusters identified. RESULTS:Given the remarkable structural and functional diversity displayed by known TOMMs, a comprehensive bioinformatic study to catalog and classify the entire RiPP class was undertaken. Here we report the bioinformatic characterization of nearly 1,500 TOMM gene clusters from genomes in the European Molecular Biology Laboratory (EMBL) and the European Bioinformatics Institute (EBI) sequence repository. Genome mining suggests a complex diversification of modification enzymes and precursor peptides to create more than 20 distinct families of TOMMs, nine of which have not heretofore been described. Many of the identified TOMM families have an abundance of diverse precursor peptide sequences as well as unfamiliar combinations of modification enzymes, signifying a potential wealth of novel natural products on known and unknown biosynthetic scaffolds. Phylogenetic analysis suggests a widespread distribution of TOMMs across multiple phyla; however, producers of similar TOMMs are generally found in the same phylum with few exceptions. CONCLUSIONS:The comprehensive genome mining study described herein has uncovered a myriad of unique TOMM biosynthetic clusters and provides an atlas to guide future discovery efforts. These biosynthetic gene clusters are predicted to produce diverse final products, and the identification of additional combinations of modification enzymes could expand the potential of combinatorial natural product biosynthesis.

Dataset Information

Bistratamides M and N, Oxazole-Thiazole Containing Cyclic Hexapeptides Isolated from Lissoclinum bistratum Interaction of Zinc (II) with Bistratamide K.

Publications

Bistratamides M and N, Oxazole-Thiazole Containing Cyclic Hexapeptides Isolated from Lissoclinum bistratum Interaction of Zinc (II) with Bistratamide K.

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