Serratiomycins D1–D3, Antibacterial Cyclic Peptides from a Serratia sp. and Structure Revision of Serratiomycin

Serratiomycin (1) is an antibacterial cyclic depsipeptide, first discovered from a Eubacterium culture in 1998. This compound was initially reported to contain l-Leu, l-Ser, l-allo-Thr, d-Phe, d-Ile, and hydroxydecanoic acid. In the present study, 1 and three new derivatives, serratiomycin D1–D3 (2–4), were isolated from a Serratia sp. strain isolated from the exoskeleton of a long-horned beetle. The planar structures of 1–4 were elucidated by using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparison of the NMR chemical shifts and the physicochemical data of 1 to those of previously reported serratiomycin indeed identified 1 as serratiomycin. The absolute configurations of the amino units in compounds 1–4 were determined by the advanced Marfey's method, 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate derivatization, and liquid chromatography–mass spectrometric (LC–MS) analysis. Additionally, methanolysis and the modified Mosher's method were used to determine the absolute configuration of (3R)-hydroxydecanoic acid in 1. Consequently, the revised structure of 1 was found to possess d-Leu, l-Ser, l-Thr, d-Phe, l-allo-Ile, and d-hydroxydecanoic acid. In comparison with the previously published structure of serratiomycin, l-Leu, l-allo-Thr, and d-Ile in serratiomycin were revised to d-Leu, l-Thr, and l-allo-Ile. The new members of the serratiomycin family, compounds 2 and 3, showed considerably higher antibacterial activities against Staphylococcus aureus and Salmonella enterica than compound 1.