Indigomycin, a new pyridinetrione from Streptomyces albus J1074 harboring the indigoidine biosynthetic gene cluster.

Heterologous expression of the indigoidine biosynthetic gene cluster from Streptomyces laurentii ATCC 31255 in Streptomyces albus J1074 resulted in the production of the known blue pigment indigoidine, along with a structurally novel pyridinetrione derivative designated indigomycin (1). The structure of indigomycin was determined through comprehensive 1D and 2D NMR spectroscopy and X-ray crystallographic analysis. Antimicrobial evaluation revealed that indigomycin (1) exhibits modest activity against methicillin-resistant Staphylococcus aureus ATCC 43300, with a minimum inhibitory concentration (MIC) of 32 μg mL-1. Biosynthetically, the pathway is proposed to be initiated by a single multi-domain NRPS (IgoA) that activates L-glutamine and directs the divergent assembly of both indigoidine and indigomycin from a common dehydroglutaminyl intermediate. This work not only enriches the structural diversity of pyridinetrione-type natural products but also presents an efficient biosynthetic strategy for sustainable production of indigoidine-based pigments.