Bacillibactin and Bacillomycin Analogues with Cytotoxicities against Human Cancer Cell Lines from Marine Bacillus sp PKU-MA00093 and PKU-MA00092

Nonribosomal peptides from marine Bacillus strains have received considerable attention for their complex structures and potent bioactivities. In this study, we carried out PCR-based genome mining for potential nonribosomal peptides producers from our marine bacterial library. Twenty-one positive strains were screened out from 180 marine bacterial strains, and subsequent small-scale fermentation, HPLC and phylogenetic analysis afforded Bacillus sp. PKU-MA00092 and PKU-MA00093 as two candidates for large-scale fermentation and isolation. Ten nonribosomal peptides, including four bacillibactin analogues (1-4) and six bacillomycin D analogues (5-10) were discovered from Bacillus sp. PKU-MA00093 and PKU-MA00092, respectively. Compounds 1 and 2 are two new compounds and the H-1 NMR and C-13 NMR data of compounds 7 and 9 is first provided. All compounds 1-10 were assayed for their cytotoxicities against human cancer cell lines HepG2 and MCF7, and the bacillomycin D analogues 7-10 showed moderate cytotoxicities with IC50 values from 2.9 +/- 0.1 to 8.2 +/- 0.2 mu M. The discovery of 5-10 with different fatty acid moieties gave us the opportunity to reveal the structure-activity relationships of bacillomycin analogues against these human cancer cell lines. These results enrich the structural diversity and bioactivity properties of nonribosomal peptides from marine Bacillus strains.