Discovery of Aburatubolactams Reveals Biosynthetic Logic for Distinct 5/5-Type Polycyclic Tetramate Macrolactams

A known polycyclic tetramate macrolactam (aburatubolactam C, 3) and three new ones (aburatubolactams D-F, 4-6, respectively) were isolated from the marine-derived Streptomyces sp. SCSIO 40070. The absolute configuration of 3 was established by X-ray analysis. A combinatorial biosynthetic approach unveiled biosynthetic enzymes dictating the formation of distinct 5/5-type ring systems (such as C-7-C-14 cyclization by AtlB1 in 5 and C-6-C-13 cyclization by AtlB2 in 6) in aburatubolactams.