Elucidation of novel turnagainolides and their biosynthetic gene cluster in Bacillus subtilis

作者：Jing Li, Shuang Han, Min Wang, Xuejiao Zhang, Shuai Zhi, Meiling Jin, Jouni Jokela, Shan He, Liwei Liu · 发表于：Applied and Environmental Microbiology · 年份：2025 · DOI：10.1128/aem.02574-24 · 被引用次数：3 · 研究领域：Microbial Natural Products and Biosynthesis、Marine Sponges and Natural Products、Antimicrobial Peptides and Activities

ABSTRACT Turnagainolides represent a unique class of cyclic depsipeptides characterized by the presence of a rare ( E )-3-hydroxy-5-phenylpent-4-enoic acid (Hppa) residue, exhibiting diverse bioactivities. While previous studies have identified turnagainolides and their congeners from various microorganisms, including Microascus , Bacillus , Arthrobacter , and Streptomyces , their biosynthetic gene cluster and pathways remained elusive. Here, we uncovered four novel compounds, turnagainolide congeners D-G ( 3–6 ), and two known compounds, turnagainolides A-B ( 1, 2 ), from Bacillus subtilis LP. Their chemical structures were elucidated through a combination analysis of LC-MS analysis, NMR spectroscopy, and the Mosher derivatization technique. To investigate their biosynthetic gene cluster, comprehensive genome sequencing, phylogenetic analysis, and anti-SMASH-based prediction were conducted, and gene knockout experiments confirmed the correlation between the tur -BGC and the biosynthesis of these compounds. The alignment of protein sequences encoded by tur -BGC against public protein databases revealed homologous proteins exclusively in Bacillus species. These findings not only expand the chemical diversity of cyclic peptides in Bacillus but also provide critical insights into the biosynthetic pathway of turnagainolides and their evolutionary lineage. IMPORTANCE Microbial natural products represent an invaluable resource in drug discovery, providing a vast reservoir of struct...