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At least 253 records · Page 14Linked to original sources
PubMed2002

Characterization of surfactin-like cyclic depsipeptides synthesized by Bacillus pumilus from ascidian Halocynthia aurantium.

A marine bacterium (KMM 1364), identified as Bacillus pumilus, was isolated from the surface of ascidian Halocynthia aurantium. Structural analysis revealed that the strain KMM 1364 produced a mixture of lipopeptide surfactin analogs with major components with molecular masses of 1035, 1049, 1063, and 1077. The variation in molecular weight represents changes in the number of methylene groups in the lipid and/or peptide portions of the compounds. Structurally, these lipopeptides differ from surfactin in the substitution of the valine residue in position 4 by leucine, and have been isolated as two carboxy-terminal variants, with valine or isoleucine in position 7. As constituents of the lipophilic part of the peptides, only beta-hydroxy-C(15)-, beta-hydroxy-C(16)-, and a high amount of beta-hydroxy-C(17) fatty acid were determined.

Journal Article↗
PubMed1983

Mechanism of depsipeptide formation catalyzed by enniatin synthetase.

Covalently bound intermediates of enniatin B synthesis could be isolated from enniatin synthetase by treatment with performic acid. By comparison with products of mild alkaline cleavage of authentic enniatin B they could be identified as the dipeptide D-2-hydroxyisovaleryl-N-methylvaline and the corresponding tetrapeptide. Synthesis of enniatins apparently proceeds via condensation of dipeptides. This was confirmed by the use of the substrate analogue isovaleric acid, which has shown to be a strong inhibitor for enniatin synthesis by formation of N-isovaleryl-N-methyl valine.

Anti-Bacterial Agents↗
PubMed2004

YM-254890 analogues, novel cyclic depsipeptides with Galpha(q/11) inhibitory activity from Chromobacterium sp. QS3666.

The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890. Their structures were determined by one- and two-dimensional NMR studies and mass spectrometry. Among these compounds, two natural analogues 2-3 which possessed acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1. This indicates that the acyl beta-HyLeu residue plays an important role in activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha residue is not critical to activity. The other hydrogenated derivative 5 had significantly less activity, which could be attributed to conformational differences.

Adenosine Diphosphate↗
PubMed2004

RA-VII, a cyclic depsipeptide, changes the conformational structure of actin to cause G2 arrest by the inhibition of cytokinesis.

In L1210 cells, RA-VII (0.1-100 nM) caused the concentration-dependent inhibition of the proliferation and G2 arrest. Treatment of PC12 cells with 10 nM RA-VII changed cell shape round with binucleation, suggesting the inhibition of cytokinesis. The fluorescence intensity of FITC-phalloidin bound to F-actin was enhanced by RA-VII. In surface plasmon resonance experiments, the signal of F-actin was modified by RA-VII in close agreement with a concentration of FITC-phalloidin binding to F-actin. These results suggest that RA-VII causes the conformational change of F-actin and the stabilization of actin filaments to induce G2 arrest.

Actins↗
PubMed1991

Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA.

Vancomycin resistance in Enterococcus faecium BM4147 is mediated by vancomycin resistance proteins VanA and VanH. VanA is a D-alanine:D-alanine ligase of altered substrate specificity [Bugg, T. D. H., Dutka-Malen, S., Arthur, M., Courvalin, P., & Walsh, C. T. (1991) Biochemistry 30, 2017-2021], while the sequence of VanH is related to those of alpha-keto acid dehydrogenases [Arthur, M., Molinas, C., Dutka-Malen, S., & Courvalin, P. (1991) Gene (submitted)]. We report purification of VanH to homogeneity, characterization as a D-specific alpha-keto acid dehydrogenase, and comparison with D-lactate dehydrogenases from Leuconostoc mesenteroides and Lactobacillus leichmanii. VanA was found to catalyze ester bond formation between D-alanine and the D-hydroxy acid products of VanH, the best substrate being D-2-hydroxybutyrate (Km = 0.60 mM). The VanA product D-alanyl-D-2-hydroxybutyrate could then be incorporated into the UDPMurNAc-pentapeptide peptidoglycan precursor by D-Ala-D-Ala adding enzyme from Escherichia coli or by crude extract from E. faecium BM4147. The vancomycin binding constant of a synthetic modified peptidoglycan analogue N-acetyl-D-alanyl-D-2-hydroxybutyrate (Kd greater than 73 mM) was greater than 1000-fold higher than the binding constant for N-acetyl-D-alanyl-D-alanine (Kd = 54 microM), partly due to the disruption of a hydrogen bond in the vancomycin-target complex, thus providing a molecular rationale for high-level vancomycin resistance.

Amino Acid Sequence↗
PubMed2002

Characterization of the surfactin synthetase C-terminal thioesterase domain as a cyclic depsipeptide synthase.

The C-terminal thioesterase domain of the nonribosomal peptide synthetase producing the lipopetide surfactin (Srf TE) retains autonomous ability to generate the cyclic peptidolactone skeleton of surfactin when provided with a soluble beta-hydroxy-butyryl-heptapeptidyl thioester substrate. Utilizing the recently solved crystal structure [Bruner, S. D., et al. (2002) Structure 10, 301-310], the active-site nucleophile, Ser80, was changed to Cys, and the other members of the catalytic triad, Asp107 and His207, were changed to Ala, with the resulting mutants lacking detectable activity. Two cationic side chains in the active site, Lys111 and Arg120, were changed to Ala, causing an increased partitioning of the product to hydrolysis, as did a P26G mutant, mimicking the behavior of lipases. To evaluate recognition elements in substrates used by Srf TE, alterations to the fatty acyl group, the heptapeptide, and the thioester leaving group were made, and the resulting substrates were characterized for kinetic competency and flux of product to cyclization or hydrolysis. Alterations that could be accepted for cyclization were identified in all three parts of the substrate, although tolerance limits for changes varied. In addition, cocrystal structures of Srf TE with dipeptidyl boronate inhibitors were solved, illustrating the critical binding determinants of the substrate. On the basis of the structures and biochemical data, the cyclizing conformation of the surfactin peptide was modeled into the enzyme active site.

Amino Acid Sequence↗
PubMed1995

Halicylindramides A-C, antifungal and cytotoxic depsipeptides from the marine sponge Halichondria cylindrata.

Halicylindramides A-C (1-3) have been isolated from the Japanese marine sponge Halichondria cylindrata. They are tetradecapeptides with the N-terminus blocked by a formyl group and the C-terminus lactonized with a threonine residue. Their total structures including absolute stereochemistry were determined by a combination of spectral and chemical methods. Halicylindramides A-C were antifungal against Mortierella ramanniana and cytotoxic against P388 murine leukemia cells.

Amino Acid Sequence↗
PubMed1997

Design, Synthesis, and Evaluation of a Depsipeptide Mimic of Tendamistat.

The cyclic hexadepsipeptide framework of enniatin B was identified as a template matching the beta-turn tripeptide of tendamistat. The modified analog 1 was synthesized as a tendamistat mimic and compared to the acyclic derivative 2 and the tripeptide Ac-Try-Arg-Tyr-OMe. These compounds were assembled from the dimeric esters 3-5. As an inhibitor of alpha-amylase, 1 is twice as potent as 2 and comparable to the tripeptide. NMR studies of 1 reveal four conformers in equilibrium in a 50:25:15:10 ratio; the ring conformation of the major component is similar to that of the enniatin B template, with the cis geometry of the alpha-hydroxyisovaleryl-N-methylvaline amide linkage; the other conformers differ in the position or presence of the cis amide linkage.

Journal Article↗