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 (3 R )-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 .