Novel Tetrapeptides, Tengupeptins A and B, Produced by Lecanicillium aphanocladii FKI-9593 Fungal Strain

The discovery of novel natural products through the exploration of distinct microorganisms is crucial for advancing drug discovery research. In this study, we focus on a unique environmental resource, microbial masses known as "Tengu-no-Mugimeshi." From the culture broth of Lecanicillium aphanocladii FKI-9593, isolated from Tengu-no-Mugimeshi collected at Mount Kurohime, Nagano Prefecture, Japan, we report the isolation of two novel tetrapeptides, tengupeptins A (1) and B (2), as well as the known compound oosporein. Structural analysis revealed that tengupeptins are composed of four amino acids: L-glutamic acid for 1 (or L-pyroglutamic acid for 2), (Z)-α,β-didehydro tryptophan (ΔZTrp), (Z)-α,β-didehydro-phenylalanine (ΔZPhe), and L-aspartic acid. Notably, dehydroamino acids containing an aromatic moiety conjugated with a double bond connected via two or more consecutive linkages are rare in natural products, and the ΔZTrp-ΔZPhe fragment represents the first example. The isolation of secondary metabolites from filamentous fungi inhabiting unique environments, such as Tengu-no-Mugimeshi, is anticipated to offer significant potential for future research.