Pentaminomycins C-E: Cyclic Pentapeptides as Autophagy Inducers from a Mealworm Beetle Gut Bacterium

Area of Science:

• Microbiology
• Natural Product Chemistry
• Molecular Biology

Background:

• The gut microbiome of insects, such as the mealworm beetle (Tenebrio molitor), is a rich source of novel microbial natural products.
• Streptomyces species are known producers of diverse bioactive secondary metabolites, including cyclic peptides.

Purpose of the Study:

• To isolate and characterize novel cyclic pentapeptides from Streptomyces sp. GG23.
• To elucidate the biosynthetic pathways and structural variations of the isolated compounds.
• To evaluate the biological activities of the novel pentapeptides.

Main Methods:

• Isolation and purification of compounds using chromatographic techniques.
• Structure elucidation via 1D and 2D NMR and mass spectrometry.
• Determination of absolute configurations using Marfey's method and BGC analysis.
• Bioinformatic analysis of the nonribosomal peptide biosynthetic gene cluster (BGC).

Main Results:

• Isolation and structural characterization of three cyclic pentapeptides, pentaminomycins C-E (1-3), containing N5-hydroxyarginine.
• Assignment of absolute configurations of amino acid residues.
• Proposed biosynthetic pathway involving NRPS and noncanonical macrocyclization by PBP-type TE.
• Pentaminomycins C and D exhibited significant autophagy-inducing activity and cytoprotection against oxidative stress.

Conclusions:

• Pentaminomycins C-E represent a new class of cyclic pentapeptides with unique structural features.
• The study provides insights into the biosynthesis of these peptides, including noncanonical cyclization mechanisms.
• Pentaminomycins C and D demonstrate potential therapeutic applications for conditions involving oxidative stress and autophagy modulation.