Abstract
Bacillus spp. are important producers of bioactive natural products with potential applications in medicine and agriculture. Bacillus sp. SCSIO 05476 from a deep-sea sediment exhibits broad-spectrum antimicrobial activities and strong cytotoxic activity. Here, an integrative approach combining genome mining and metabolic profiling has been applied to decipher the chemical origins of this strain’s varied and significant biological activities. First, genome mining revealed 19 candidate gene clusters encoding the biosynthesis of diverse secondary metabolites. Then, a series of bacillibactins, fengycins, bacillomycins, surfactins, bacillaenes, macrolactins, and related species were found by LC-DAD-MS. Finally, three new linear bacillibactins, linbacillibactins A–C (1–3), along with 11 known secondary metabolites, bacillibactin (4), normal-C13 Val7 surfactin (5), anteiso-C13 Leu7 surfactin (6), iso-C14 Leu7 surfactin (7), normal-C14 Leu7 surfactin (8), anteiso-C14 Leu7 surfactin (9), macrolactin D (10), normal-C14 bacillomycin D (11), iso-C16 bacillomycin D (12), normal-C17 bacillomycin D (13), and iso-C17 bacillomycin D (14), were obtained and elucidated by bioactivity and structure-guided isolation from the fermentation of strain SCSIO 05746. Among them, new compounds 1–3 show significant siderophore activities comparable to that of bacillibactin (4), compounds 13 and 14 exhibit strong cytotoxic activity. At the same time, the strain classification status was confirmed by genomic analyses, and the complete genome sequence of Bacillus siamensis was presented firstly. This study provides a foundation for understanding the mechanisms driving SCSIO 05746’s multiple bioactivities and demonstrates a successful way of discovering bioactive metabolites using a combination of genome mining and metabolic profiling methods.
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Acknowledgments
We are also truly grateful to Ms. Sun, Ms. Xiao, Ms. Zhang, and Mr. Li of the analytical facility of the South China Sea Institute of Oceanology for recording NMR and MS spectra.
Funding
This research was supported by the National Natural Science Foundation of China (41576136, 81425022, 31872036 and U1501223), the Key Laboratory of Tropical Marine Bio-resources and Ecology Program of CAS (LMB151005), the Science and Technology Innovation Program for the Youth Talents of Shenyang (RC170266), and the Youth Innovation Promotion Association CAS (2018229).
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Pan, H., Tian, X., Shao, M. et al. Genome mining and metabolic profiling illuminate the chemistry driving diverse biological activities of Bacillus siamensis SCSIO 05746. Appl Microbiol Biotechnol 103, 4153–4165 (2019). https://doi.org/10.1007/s00253-019-09759-2
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DOI: https://doi.org/10.1007/s00253-019-09759-2