Discovery of a Fungal HR-PKS Cluster Encoding Biosynthetic Pathways for Macrolides with Two Distinct Ring Sizes
Abstract
Through the heterologous expression of a highly reducing polyketide synthase and a thioesterase from the apeml cluster, a putative macrolide biosynthetic gene cluster on the genome of Aspergillus petrakii, we obtained a naturally new 10-membered macrolide (1) and recifeiolide (2), a known 12-membered macrolide. To obtain modified macrolides, feeding experiments using Aspergillus oryzae transformants expressing individual modification enzymes were employed, resulting in the isolation of aspinolide A (3) and 2 new macrolides, petrakilides A (4) and B (5). These findings highlight a promiscuous enzymatic cascade capable of generating macrolides with distinct scaffolds and different ring sizes.
Fields of Study & Subjects
Microbial Natural Products and Biosynthesis
Synthetic Organic Chemistry Methods
Fungal and yeast genetics research
Publication details
- Journal / source
- Chemical and Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Volume
- 74
- Issue
- 1
- Pages
- 64–70
- Publication date
- 9 January 2026
- Language
- EN