Galbonolide A

Galbonolide A, also known by aliases such as rustmicin and erythronolide A, 6,7,10,11,12,20-hexadehydro-6-demethyl-9-deoxo-3,5,11,12-tetradeoxy-4,17-dihydroxy-6-O-methyl-3-oxo , is a naturally occurring 14-membered macrolide antibiotic with significant biological activity. Its unique chemical structure is defined by the systematic name (3R,7Z,9S,12E,14S)-14-ethyl-5-hydroxy-5-(hydroxymethyl)-7-methoxy-3,9,13-trimethyl-11-methylidene-1-oxacyclotetradeca-7,12-diene-2,4-dione, with a molecular formula of C₂₁H₃₂O₆ and a molecular weight of 380.475.
Originally identified as an inhibitor of wheat rust fungus, Galbonolide A was later found to exhibit potent antifungal activity against clinically relevant pathogenic strains, including Candida albicans and Cryptococcus neoformans. Its biosynthesis originates from bacterial sources, specifically produced by Streptomyces galbus and related Streptomyces strains such as Streptomyces sp. SR107. The biogenesis process is guided by a unique single-module, highly reducing type I polyketide synthase (PKS) system, which enables iterative assembly of propionates with precisely programmed β-keto group modifications—a distinct biochemical strategy for polyketide synthesis.
A key breakthrough in understanding its mechanism came from research at Merck Research Laboratories, which revealed that Galbonolide A exerts its fungicidal effects by inhibiting inositol phosphoceramide (IPC) synthase. This enzyme is critical for fungal sphingolipid biosynthesis, and its inhibition leads to ceramide accumulation in growing cells, ultimately resulting in cell death. Notably, mammalian sphingolipid biosynthesis lacks a corresponding enzyme, suggesting potential selective toxicity that minimizes harm to host cells.

Offers a novel antifungal mechanism of action via IPC synthase inhibition, distinguishing it from conventional antifungals and addressing potential resistance concerns.
Enables selective biological activity: the absence of homologous IPC synthase in mammalian cells supports a favorable toxicity profile for research applications.
Serves as a valuable lead compound for chemical modification: its core structure can be modified (e.g., at the C-6 position) to explore structure-activity relationships (SAR) and improve stability.
Comes with comprehensive characterization data, including CAS number (100227-57-4), InChI keys, and exact mass (380.21988874), ensuring reproducibility in experimental use.
Facilitates multi-disciplinary research: bridging natural product chemistry, microbiology, and pharmacology due to its biosynthesis pathway and biological targets.

Antifungal Drug Discovery: Used as a prototype compound to study IPC synthase inhibitors, aiding in the design of new antifungal agents with improved stability and potency.
Microbiology Research: Employed to investigate sphingolipid biosynthesis in pathogenic fungi like Candida and Cryptococcus spp., including ceramide accumulation and cell death pathways.
Biochemical Mechanism Studies: Serves as a tool to validate IPC synthase function in fungal metabolism and explore cross-talk with other lipid biosynthesis pathways.
Synthetic Chemistry: Acts as a template for developing analogues—researchers have used its structure to synthesize modified derivatives (e.g., methylthio-substituted analogues) and key intermediates via conjugated diene system construction.
Natural Product Biosynthesis Research: Enables investigation of unusual single-module type I PKS systems in Streptomyces, advancing understanding of polyketide assembly.

In the field of IPC synthase-targeting antifungals and 14-membered macrolide research, related products of interest include Aureobasidin A—a cyclic depsipeptide with broad-spectrum antifungal activity against Candida spp., Cryptococcus neoformans, and some Aspergillus spp.—and Khafrefungin, an aldonic acid ester active against C. albicans and Saccharomyces cerevisiae. Additionally, Galbonolide B (neorustmicin)—a structural homologue differing in precursor incorporation during biosynthesis—and synthetic galbonolide analogues (e.g., C-6 modified derivatives) are relevant for comparative studies. If you are interested in related products, you can directly contact us or use our product customization service.