Genome Mining and Enzymatic Total Biosynthesis of Purincyclamide

A cyclodipeptide synthase-containing gene cluster (pcm) was identified in Streptomyces chrestomyceticus NA4264 through genome mining. Heterologous expression of the cryptic pcm gene cluster in Streptomyces albus led to the production of a new highly modified cyclodipeptide named purincyclamide (1). Bioinformatic analysis and gene knockout experiments revealed the biosynthetic pathway. The production of 1 was achieved through a one-pot enzymatic reaction.