2020/08/11 by Zhuan Zhang, Tianzhang Qiao, Kenji Watanabe +1 · 1 citation
Chemistry · Medicine · Biochemistry, Genetics and Molecular Biology · #Chemical synthesis and alkaloids #Microbial Natural Products and Biosynthesis #Synthesis and Biological Activity
paper · pdf · doi:10.1002/anie.202008321
openalex publication_date 2020/08/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, and can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway of compounds in the citridone family through heterologous reconstitution of the pfp pathway. We demonstrate that multiple members of this family can be accessed from a reactive ortho-quinone methide (o-QM) intermediate through electrocyclization, cycloisomerization, or conjugate addition. Formation of the quaternary carbon center in citridone B is catalyzed by an epoxide-forming P450 enzyme, followed by carbon skeletal rearrangement. Our results showcase how nature harvests the reactivities of an o-QM intermediate to biosynthesize complex natural products.