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

Abstract

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.