Identification of the actinorhodin monomer and its related compound from a deletion mutant of the actVA-ORF4 gene of Streptomyces coelicolor A3(2)

An oxygenated derivative of dihydrokalafungin (DHK) was isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of a dimeric benzoisochromanequinone (BIQ) antibiotic, actinorhodin (ACT), in Streptomyces coelicolor A3(2). Spectroscopic analysis elucidated its structure as 8-hydroxy-DHK, corresponding to the monomeric unit of ACT. Further metabolite analysis identified its related compound, clearly derived from the reduction of 8-hydroxy-DHK. The structures of these metabolites indicate the essential role of ActVA-ORF4 in ACT biosynthesis, specifically in dimerization of a BIQ intermediate via C–C bond formation.

8-Hydroxy-dihydrokalafungin (6) and its reduced form (7) have been isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of actinorhodin (ACT) in Streptomyces coelicolor A3(2). Their structures correspond to the monomeric unit of ACT, and indicate a new possibility of (8) as the intermediate for the dimerization step in ACT biosynthesis.Figure optionsDownload as PowerPoint slide