Antimicrobial Lobophorins from Endophytic Strain Streptomyces sp. R6 Obtained from Azadirachta indica

Endophytic bacteria are an important source for developing antimicrobial substances. With the aim to find eco-friendly antimicrobial agents from natural sources, <i>Streptomyces</i> sp. R6 was isolated from <i>Azadirachta indica</i>. After that, a new spirotetronate natural product, lobophorin S (compound <b>2</b>), together with lobophorin H8 (compound <b>1</b>) and a known macrolide compound divergolide C (compound <b>3</b>) were isolated from the cultural solution of strain R6. These compounds mark the first isolation of marine-derived microbial natural products known as lobophorins (LOBs) from endophytic bacteria. The structures of these three compounds were identified by extensive NMR and HRMS analyses. The antimicrobial activities of these three compounds against eight fungal and four bacterial phytopathogens were separately evaluated. Compound <b>1</b> demonstrated better antibacterial activity against <i>Erwinia carotovora</i>, <i>Pseudomonas syringae</i> pv. tomato, and <i>P. syringae</i> pv. lachrymans with MIC values of 3.91, 7.81, and 15.63 μg/mL, respectively. Additionally, compounds <b>1</b>-<b>3</b> all showed antifungal activity against <i>Botrytis cinerea</i>, with the MIC values of 1.95, 7.81, and 15.63 μg/mL, respectively. Notably, the <i>in vivo</i> antifungal effect of <b>1</b> against <i>B. cinerea</i> was up to 78.51 ± 3.80% at 1.95 µg/mL, significantly surpassing polyoxin B (70.70 ± 3.81%). These results highlight the potential of lobophorins as promising lead compounds for the development of new, sustainable agents to control plant diseases.