Spirocyclic β-lactone secondary metabolites modulate spliceosome function - PubMed
10 hours ago
- #natural product discovery
- #spliceosome modulation
- #alternative splicing
- Spirocyclic β-lactones (SβLs) are natural products with potent cytotoxicity and an unknown mechanism, produced by actinomycetota.
- Study isolated SβLs from Streptomyces platensis, including a new variant, linking them to the oxazolomycin D (OxD) family via a cryptic gene cluster.
- SβLs have two pharmacophores: a polyketide component for target engagement and a β-lactone warhead for cytotoxicity.
- OxD treatment interacts with spliceosome proteins, validated by alternative splicing changes, suggesting therapeutic potential in cancers with aberrant splicing.