Seongsanamides A–D: Antiallergic Bicyclic Peptides from Bacillus safensis KCTC 12796BP

Abstract

Six seongsanamides were isolated from the culture broth of Bacillus safensis KCTC 12796BP, and their structures were elucidated by spectroscopic data analysis combined with Marfey's method, electronic circular dichroism calculations, and biosynthetic gene cluster analysis. Compounds 1−4 were bicyclic peptides with isodityrosine residues; 5 and 6 were monocyclic peptides. Only the bicyclic seongsanamides inhibited degranulation and LTC 4 /PGD 2 generation in IgE/Ag-stimulated bone marrow-derived mast cells. Oral administration of 1 suppressed mast cell-dependent passive cutaneous anaphylaxis reaction.

In Vitro Metabolism Study of Seongsanamide A in Human Liver Microsomes Using Non-Targeted Metabolomics and Feature-Based Molecular Networking

“…Seongsanamide A is a cyclic depsipeptide with a peptide linkage, and it is easily protonated in a positive ionization mode. Therefore, the positive ionization mode was selected, which was consistent with previous studies [ 7 ].…”

“…Seongsanamide A (>98%, Figure 1 ) was isolated from the fermentation broth extracts of Bacillus sp. KCTC 12796BP by as previously reported [ 7 ]. Acetaminophen, amodiaquine, bupropion, chlorzoxazone, dextromethorphan, trimipramine, uridine diphosphoglucuronic acid (UDPGA), nicotinamide adenine dinucleotide phosphate (NADP + ), glucose-6-phosphate (G6P), and G6P dehydrogenase (G6PDH) were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

“…It contains a unique isodityrosine moiety which is responsible for its bioactivity [8]. This compound showed potent antiallergenic activities by suppressing leukotriene C4 production, and Pharmaceutics 2021, 13, 1031 2 of 13 β-hexosaminidase release in bone marrow-derived mast cells without significant cytotoxicity, even at 100 µM [7]. In addition, it displays comparable anti-allergic properties with fexofenadine, a known H-1 blocker, after oral administration in a passive cutaneous anaphylaxis mouse model [7].…”

“…This compound showed potent antiallergenic activities by suppressing leukotriene C4 production, and Pharmaceutics 2021, 13, 1031 2 of 13 β-hexosaminidase release in bone marrow-derived mast cells without significant cytotoxicity, even at 100 µM [7]. In addition, it displays comparable anti-allergic properties with fexofenadine, a known H-1 blocker, after oral administration in a passive cutaneous anaphylaxis mouse model [7]. In 2020, Ye and coworkers reported the total synthesis of seongsanamide A using intramolecular Chan-Evans-Lam coupling and Miyuara borylation [8].…”

“…The genus Bacillus in the marine environment is known to produce structurally diverse peptides, including bicyclic peptides. Seongsanamide A ( Figure 1 ) is one of four bioactive bicyclic depsipeptides isolated from Bacillus safensis KCTC 12796BP, which was obtained from a marine sponge collected from Seongsan on Jeju Island, Korea [ 7 ]. It contains a unique isodityrosine moiety which is responsible for its bioactivity [ 8 ].…”