Abstract 2777 The effect of Opuntia ficus-indica on glucose uptake in cells

Natamycin, a glycosylated polyene macrolide (GPM), is widely used as an antifungal agent in food preservation, particularly in dairy products, and as a treatment for fungal eye infections.While ergosterol has been established as natamycin's therapeutic target, the structural mechanisms underlying ergosterol binding and extraction remain poorly understood.Recent bioinformatics analysis suggests that natamycin, like amphotericin B, self-assembles into a "sterol-contained sponge," a property attributed to the highly conserved hemiketal region.In this study, we developed a high-yield biosynthetic protocol to produce uniformly 13C-enriched natamycin, enabling structural investigations using solid-state NMR.Structural analyses reveal the formation of an ergosterol-binding sponge, consistent with the model in which natamycin aggregates extract ergosterol from fungal membranes and incorporate it into void volumes within the sponge.These findings refine our understanding of natamycin's mechanism of action and provide new insights for antifungal drug development.

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Publication Details

Journal
Journal of Biological Chemistry
Published
2025-05-01
DOI
https://doi.org/10.1016/j.jbc.2025.109082
Primary Topic
Botanical Research and Applications
Type
article
Field-Weighted Citation Impact
0.00

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article

Abstract 2777 The effect of Opuntia ficus-indica on glucose uptake in cells

Mary Lares, Kevin Witt
Journal of Biological Chemistry
Botanical Research and Applications
article

Abstract 2777 The effect of Opuntia ficus-indica on glucose uptake in cells

Mary Lares, Kevin Witt
article en

Abstract

Natamycin, a glycosylated polyene macrolide (GPM), is widely used as an antifungal agent in food preservation, particularly in dairy products, and as a treatment for fungal eye infections.While ergosterol has been established as natamycin's therapeutic target, the structural mechanisms underlying ergosterol binding and extraction remain poorly understood.Recent bioinformatics analysis suggests that natamycin, like amphotericin B, self-assembles into a "sterol-contained sponge," a property attributed to the highly conserved hemiketal region.In this study, we developed a high-yield biosynthetic protocol to produce uniformly 13C-enriched natamycin, enabling structural investigations using solid-state NMR.Structural analyses reveal the formation of an ergosterol-binding sponge, consistent with the model in which natamycin aggregates extract ergosterol from fungal membranes and incorporate it into void volumes within the sponge.These findings refine our understanding of natamycin's mechanism of action and provide new insights for antifungal drug development.

Journal of Biological ChemistryVol. 301(5)
University of Wisconsin System (US), University of Wisconsin–Madison (US), Sonoma State University (US)
National Institutes of Health
Zero hunger
Openalex Percentile: Top 84%
Botanical Research and Applications
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