Discovery, Biosynthesis, and Heterologous Production of Streptoseomycin, an Anti-Microaerophilic Bacteria Macrodilactone

Streptoseomycin (1), which is a rare macrodilactone with potent activities against microaerophilic bacteria, featuring a pentacyclic 5/14/10/6/6 ring system together with an ether bridge, was characterized by a combination of spectroscopic method and X-ray analysis from a marine Streptomyces seoulensis. Sequencing and characterization of a ∼76-kb biosynthetic gene cluster led to the proposition of the biosynthetic pathway of 1. Heterologous expression of the gene cluster using a BAC vector in Streptomyces chartreusis 1018 led to the successful production of 1.