Sequences of Tolypins, Insecticidal Efrapeptin‐Type Peptaibiotics from Species of the Fungal Genus Tolypocladium

Abstract

A peptide mixture named tolypin, originally isolated from species of the fungal genus Tolypocladium, was structurally characterised and sequences compared to those reported for efrapeptins isolated from strains of Tolypocladium inflatum. Chiral amino acid analysis, direct infusion, and online HPLC electrospray ionization tandem mass spectrometry provided composition, molecular weights of peptides, and series of diagnostic fragment ions. Sequences deduced from ESI‐MS revealed that tolypins C−G are identical to efrapeptins C−G. The results were corroborated by ESI‐MS and HPLC of an authentic efrapeptin sample from Eli Lilly Research Laboratories (USA). Comparison of the HPLC elution profiles of efrapeptin and tolypin indicated a pronounced microheterogeneity of the former. A high‐resolution HPLC of authentic efrapeptin has not been published before. Close relationship and partial identity of sequences of tolypins and efrapeptins, which had previously been postulated, were definitely proven. The geographical origin of the two most important T. inflatum strains used for sequencing of efrapeptins/tolypins could unambiguously be clarified. A new minor compound, designated tolypin H1, was sequenced. High proportions of helicogenic Aib (α‐aminoisobutyric acid) and l‐isovaline, N‐terminal acetyl‐l‐pipecolic acid and the unusual, amide‐bound C‐terminal residue, named (S)‐2‐amino‐1‐(1,5‐diazabicyclo[4.3.0]non‐5‐ene‐5‐ylium)‐4‐methylpentane corresponding to 1‐[(2S)‐2‐amino‐4‐methylpentyl]‐2,3,4,6,7,8‐hexahydropyrrolo[1,2‐a]pyrimidin‐1‐ium, define these peptides as linear, cationic peptaibiotics.

Tolypocladamides A–G: Cytotoxic Peptaibols from Tolypocladium inflatum

“…Only cyclosporins L, P, and 27 contain the Bmt residue that we found in tolypocladamides A–E . The efrapeptins, another series of linear peptides with antifungal, insecticidal, ATPase inhibitory, and antitumor activities, have been reported from the genus Tolypocladium . ,, The characterization of a mixture of peptides named tolypins isolated from Tolypocladium species revealed that these tolypins are similar to those efrapeptins except for tolypin H1 . Elvapeptins, an added series of peptides similar to efrapeptins, have been identified from T. inflatum ; however, no sequence is reported .…”

“…15,16,28 The characterization of a mixture of peptides named tolypins isolated from Tolypocladium species revealed that these tolypins are similar to those efrapeptins except for tolypin H1. 29 Elvapeptins, an added series of peptides similar to efrapeptins, have been identified from T. inflatum; however, no sequence is reported. 30 In summary, the genus Tolypocladium is a valuable source of biologically active peptides.…”

Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications

“…Pip (4-aminopiperidine-4-carboxylic acid) is a naturally occurring amino acid found on Efrapeptin peptides, which are produced by fungi of the species Tolypocladium [ 161 ]. This class of peptides has antifungal, insecticidal, and mitochondrial ATPase inhibitory activities [ 161 , 162 ]. The right-handed α-helical structure cannot be adopted by Pip-rich peptides.…”

Perspective Chapter: Secondary Metabolites of Entomopathogens as Biotechnological Tools for the Biological Control of Agricultural Insect Pests

“…These molecules constitute a highly varied mixture of antibiotic peptides generated by some fungi, such as Tolypocladium niveun, Beauveria nivea, and Tolypocladium Perspective Chapter: Secondary Metabolites of Entomopathogens as Biotechnological Tools... DOI: http://dx.doi.org/10.5772/intechopen.111465 cylindrosporum [21]. A nonpolar extract from a culture broth of Beauveria bassiana showed toxic activity against the red potato beetle.…”