Elucidation of novel turnagainolides and their biosynthetic gene cluster in <i>Bacillus subtilis</i>

Microbial natural products represent an invaluable resource in drug discovery, providing a vast reservoir of structurally and functionally diverse compounds with promising therapeutic potential. A comprehensive understanding of natural product biosynthesis not only deepens our knowledge of their chemical complexity but also drives advancements in chemical synthesis and metabolic engineering, paving the way for the generation of novel bioactive compounds. In this study, we report that a marine axenic culture of <i>B. subtilis</i> LP synthesizes six turnagainolides (<b>1-6</b>), which exhibit both biofilm-inhibitory and cytotoxic activities. These findings expand our understanding of the structure-activity relationships of turnagainolides and offer new insights into their potential biological roles. Moreover, the identification of biosynthetic gene clusters and the proposed biosynthetic pathway provide a valuable framework for elucidating turnagainolide biosynthesis, laying the groundwork for future efforts to optimize their production and explore their applications in drug development.