Pyracrimycin A

Actinomycetes make a wealth of complex, structurally diverse natural products, and a key challenge is to link them to their biosynthetic gene clusters and delineate the reactions catalyzed by each of the enzymes. Here, we report the biosynthetic gene cluster for pyracrimycin A, a set of nine genes that includes a core nonribosomal peptide synthase (pymB) that utilizes serine and proline as precursors and a monooxygenase (pymC) that catalyzes Baeyer-Villiger oxidation. The cluster is similar to the one for brabantamide A; however, pyracrimycin A biosynthesis differs in that feeding experiments with isotope-labeled serine and proline suggest that a ring opening reaction takes place and a carbon is lost from serine downstream of the oxidation reaction. Based on these data, we propose a full biosynthesis pathway for pyracrimycin A.

Some biological characteristics of pyracrimycin A (I), a metabolic compound isolated from cultures of Streptomyces eridani are examined. Some other compounds related to I, obtained both by chemical reaction from the natural product and by synthesis are described. The in vitro antibacterial activity seems to be due to the presence of the unsaturated moiety --N equals (see article) --CH equals CH-- (see article) equals O.