Insecticidal Cyclodepsitetrapeptides from Mortierella alpina

Area of Science:

• Mycology
• Natural Product Chemistry
• Insect Toxicology

Background:

• Early diverging fungi, including *Mortierella alpina*, are recognized as sources of valuable bioactive peptides.
• Screening fungal isolates is a key strategy for discovering novel natural products with potential applications.

Purpose of the Study:

• To identify and characterize novel bioactive peptides from early diverging fungi.
• To evaluate the biological activity and safety profile of the discovered compounds.

Main Methods:

• Screening of 22 fungal isolates and precursor-directed biosynthesis.
• Structure elucidation using Nuclear Magnetic Resonance (NMR) and High-Resolution Electrospray Ionization Mass Spectrometry/Mass Spectrometry (HR-ESI-MS/MS).
• Determination of absolute configuration via Marfey's analysis and total synthesis.

Main Results:

• Identification of a new family of threonine-linked cyclotetradepsipeptides, designated cycloacetamides A-F (compounds 1-6).
• Structural confirmation and determination of absolute configurations for cycloacetamides A-F.
• Cycloacetamides demonstrated no cytotoxicity against human cells.
• High selective insecticidal activity was observed against fruit fly larvae.

Conclusions:

• *Mortierella alpina* and related fungi are promising sources for novel bioactive peptide discovery.
• Cycloacetamides represent a new class of insecticidal compounds with a favorable safety profile for human cells.
• These findings suggest potential applications for cycloacetamides in agricultural pest control.