Research and Application of the Polyene Macrolide Antibiotic Nystatin

TL;DR

This review explores nystatin, an antifungal drug, covering its chemistry, mechanism, safety, and future improvements through gene editing and synthetic biology.

Contribution

The paper highlights new gene-editing strategies, particularly CRISPR/Cas9, to improve nystatin safety and production efficiency.

Findings

Nystatin targets ergosterol in fungi and has broad antifungal activity.

Impurities like RT6 (albonoursin) can cause cardiotoxicity, emphasizing the need for quality control.

CRISPR/Cas9 is proposed to enhance nystatin production and purity by modifying biosynthesis pathways.

Abstract

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A1 via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application.

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