Work

Paraisariamides: Cycloheptapeptide Toxins from Entomopathogenic Fungi ( Paraisaria spp.) That Inhibit Total Protein Synthesis

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Insect-associated fungi are prolific producers of peptidic natural products with potent biological activities. Paraisaria is a genus of insect-pathogenic fungi (Family Ophiocordycipitaceae) in the Order Hypocreales, which also includes other Cordyceps -like fungi. Such fungi are increasingly used as functional foods and nutraceuticals, but Paraisaria may also be unintentionally consumed through infected, potentially toxic, edible insects. Here we report the discovery, isolation, and structure elucidation of paraisariamides A–D ( 1 – 4 ) from Paraisaria cascadensis and paraisariamides E–H ( 5 – 8 ) from P. insignis . Total synthesis of 1 and 5 – 8 was instrumental for comprehensive structure assignment and provided pure compounds for advanced biological testing. The paraisariamide family of N -methylated cyclic heptapeptides has been detected in all Paraisaria specimens analyzed to date from a variety of ecological niches. Paraisariamides A–H ( 1 – 8 ) display differential cell-type specific toxicity to human cancer cells, and we demonstrate that the most cytotoxic paraisariamides E–H ( 5–8 ) potently and rapidly inhibit mammalian protein synthesis. Molecular cartography was used to visualize the spatial distribution of paraisariamides in a lyophilized specimen of a beetle larva parasitized by P. insignis . Localization of paraisariamides to the fungal endosclerotium within the host larva is consistent with a role in localized disruption of host protein synthesis.

Source: Journal of Natural Products

DOI: 10.1021/acs.jnatprod.5c01111