Two Novel Hexadepsipeptides with Several Modified Amino Acid Residues Isolated from the Fungus Isaria

Abstract

Two new cyclohexadepsipeptides have been isolated from the fungus Isaria. Fungal growth in solid media yielded hyphal strands from which peptide fractions were readily isolable by organic-solvent extraction. Two novel cyclodepsipeptides, isaridin A and isaridin B, have been isolated by reverse-phase HPLC, and characterized by ESI-MS and 1H-NMR. Single crystals of both peptides have been obtained, and their 3D structures were elucidated by X-ray diffraction. The isaridins contain several unusual amino acid residues. The sequences are cyclo(beta-Gly-HyLeu-Pro-Phe-NMeVal-NMePhe) and cyclo(beta-Gly-HyLeu-beta-MePro-Phe-NMeVal-NMePhe), where NMeVal is N-methylvaline, NMePhe N-methylphenylalanine, and HyLeu hydroxyleucine (= 2-hydroxy-4-methylpentanoic acid). The two peptides differ from one another at residue 3, isaridin A having an (S)-proline at this position, while beta-methyl-(S)-proline (= (2S,3S)-2,3,4,5-tetrahydro-3-methyl-1H-pyrrole-2-carboxylic acid) is found in isaridin B. The solid-state conformations of both cyclic depsipeptides are characterized by the presence of two cis peptide bonds at HyLeu(2)-Pro(3)/HyLeu(2)-beta-MePro(3) and NMeVal(5)-NMePhe(6), respectively. In isaridin A, a strong intramolecular H-bond is observed between Phe(4)CO...HNbeta-Gly(1), and a similar, but weaker, interaction is observed between beta-Gly(1)CO...HNPhe(4). In contrast, in isaridin B, only a single intramolecular H-bond is observed between beta-Gly(1)CO...HNPhe(4).

Identification of α- and β-hydroxy acid containing cyclodepsipeptides in natural peptide mixtures using negative ion mass spectrometry

“…The formation of six oxazinones requires nucleophilic attack of the carbonyl oxygen atom of residue (5) on the carbonyl carbon of ␤-Gly 6. The molecular conformation of isaridin has been determined in crystals for two distinct members of this class of cyclodepsipeptides [13]. Significant differences have been observed in the conformation at the ␤-Gly residues in the case of isaridin A and isaridin B, as illustrated in Figure 6.…”

“…Conditions for growth of fungal cultures and extracts of hyphae have been described earlier [13,14]. The crude hyphal extract was dissolved in MeOH, centrifuged to obtain a clear solution, and subsequently used for mass spectrometry and also for reverse-phase (RP) chromatographic purification.…”

“…During the course of investigations on isarial peptides, produced by the fungus Isaria, we obtained two groups of cyclohexadepsipeptides [13,14]. The isariins contain a single ␤-hydroxy residue, while isaridins contain an ␣-hydroxy residue and a single ␤-amino acid residue.…”

“…The inset to Figure 1 illustrates fungal hyphae obtained over a solid medium, which can be directly extracted with organic solvents to yield predominantly cyclodepsipeptide libraries. The assignments of the isaridins (␣ hydroxy) and isariins (␤ hydroxy) are based on previous mass spectrometric, NMR and X-ray crystallographic investigations [13,14]. While there is a distinct difference in the molecular weight ranges of isariins and isaridins, it is evident that the higher mass components of the former and lower mass components of the latter may overlap.…”

Isolement et caractérisation morphologique de moisissures productrices de substances antibactériennes à partir d’aliments locaux au Burkina Faso

“…Les Ravindra et al (2004). L'antibiotique produit a été extrait du milieu de culture à partir du filtrat obtenu (Smaoui, 2010).…”