A genomic and spectroscopic signature-based search revealed a cycloaromatized enediyne, jejucarboside A (<b>1</b>), from a marine actinomycete strain. The structure of <b>1</b> was determined as a new cyclopenta[<i>a</i>]indene glycoside bearing carbonate functionality by nuclear magnetic resonance, high-resolution mass spectrometry (MS), MS/MS, infrared spectroscopy, and a modified Mosher's method. An iterative enediyne synthase pathway has been proposed for the putative biosynthesis of <b>1</b> by genomic analysis. Jejucarboside A exhibited cytotoxicity against the HCT116 colon carcinoma cells.