Aziridine-ring-opened azicemicins with ferroptosis inhibitory activity from the Kibdelosporangium phytohabitans XY-R10.

Genome mining of eight Kibdelosporangium genomes revealed previously untapped biosynthetic potential of diverse natural products. Among these, azicemicins, characterized by a unique aziridine moiety, drew considerable attention. Further genomic and metabolic analysis facilitated the identification of previously undescribed compounds from the K. phytohabitans XY-R10, including two angucyclines (1-2) and six azicemicins (3-8). Their structures were elucidated using comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and electronic circular dichroism. Compounds 3-8 exhibited a distinctive ring-opened aziridine, likely originating from an acetylated aziridine precursor. Notably, compound 3 exhibited significant ferroptosis inhibition by decreasing RSL3-induced HMOX1 gene expression and upregulating GCH1 gene expression.