Natural Cyclopeptaibiotics and Related Cyclic Tetrapeptides: Structural Diversity and Future Prospects

Abstract

Linearity is not considered a prerequisite anymore, and extension of the current definition of 'peptaibiotics' to cyclic, Aib-containing peptides is proposed. Sequences and bioactivities, together with ecophysiological importance of cyclopeptaibiotics and related cyclic tetrapeptides, and their fungal-taxonomic relationships, are discussed.

Two Classes of New Peptaibols Are Synthesized by a Single Non-ribosomal Peptide Synthetase of Trichoderma virens

“…Peptaibols (a subgroup of peptaibiotics) (2) are peptides characterized by short linear chain lengths (Յ20 residues), C-terminal alcohol residues, and high levels of non-standard amino acids, principally ␣-aminoisobutyric acid (Aib), 2 isovaline (Iva), and the imino acid hydroxyproline (Hyp). Naturally occurring peptaibols have been isolated from soil fungi (mostly from the genus Trichoderma (teleomorph Hypocrea) and related genera), and often exhibit antibacterial, antifungal and anti-cancer properties (3)(4)(5)(6)(7)(8)(9). The amphipathic nature of peptaibols allows them to self-associate into oligomeric ionchannel assemblies which span the width of lipid bi-layer membranes.…”

Peptaibiomics: Towards a Myriad of Bioactive Peptides Containing Cα‐Dialkylamino Acids?

“…The majority of Aib-containing peptides carries a C-terminal residue representing a 2-amino alcohol, and this subgroup is, therefore, referred to as peptaibols [2] [3]. In strongly lipophilic peptaibols, the N-terminus is acylated by octanoic, decanoic, or cis-dec-4-enoic acid, and these are named lipopeptaibols [4].…”

Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae

“…The C 18 norterpenoid ketone 152 shares a common bicyclic moiety with mycaperoxide F (137) [112], and the C 16 norterpenoid euplectellodiol (145) reflects the same bicyclic system as mycaperoxide A (138) [114]. The only comparative study to assess the biological activity of cyclic peroxides and their norterpene equivalents was that of euplectellodiol (145), which showed no cytotoxicity in contrast to its related cyclic peroxide mycaperoxide A (138), which displayed potent cytotoxicity. This provides evidence that the cyclic peroxy functionality is essential for bioactivity [114].…”

“…Cyclic peptides are commonly observed as fungal metabolites [142][143][144]. Sponges often form associations with fungi and it has been speculated that the azumamides could originate from a spongeassociated fungal source rather than the sponge itself [145]. The azumamides, and other cyclic tetrapeptides, have received interest due to their bioactivities [146].…”