Genome mining of the deep sea-derived Streptomyces atratusSCSIO ZH16 enabled the activation of a cyclodepsipeptide gene cluster and isolation of its cinnamic acid-bearing product, atratumycin (1). Atratumycin’s structure was elucidated on the basis of extensive spectroscopic experiments, X-ray data, and Marfey’s method; a plausible biosynthesis and tailoring modification of 1are also proposed and investigated. Additionally, atratumycin is active against Mycobacteria tuberculosisH37Ra and H37Rv with MICs of 3.8 and 14.6 μM, respectively.