Nomimicins B-D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura.

Zhiwei Zhang,Tao Zhou,Shun Saito,Enjuro Harunari,Taehui Yang,Keisuke Fukaya,Yasuhiro Igarashi,Daisuke Urabe,Chiaki Imada,Katsuhisa Yamada

doi:10.3762/bjoc.17.141

Abstract

Three new tetronate-class polyketides, nomimicins B, C, and D, along with nomimicin, hereafter named nomimicin A, were isolated from the culture extract of Actinomadura sp. AKA43 collected from floating particles in the deep-sea water of Sagami Bay, Japan. The structures of nomimicins B, C, and D were elucidated through the interpretation of NMR and MS analytical data, and the absolute configuration was determined by combination of NOESY/ROESY and ECD analyses. Nomimicins B, C, and D showed antimicrobial activity against Gram-positive bacteria, Kocuria rhizophila and Bacillus subtilis, with MIC values in the range of 6.5 to 12.5 μg/mL. Nomimicins B and C also displayed cytotoxicity against P388 murine leukemia cells with IC50 values of 33 and 89 μM, respectively.

Highlights

Actinomycetes are a valuable source of bioactive compounds, accounting for approximately two thirds of all known antibiotics, and more than 70% of them are produced by the genusStreptomyces [1]
In the past 20 years, our laboratory studied the actinomycetes collected from the deep sea water (DSW) of the Sea of Japan and discovered diverse classes of bioactive compounds, such as lydicamycin congeners, γ-butyrolactones, and nyuzenamides [9,10,11], whereas DSW in other sea areas had not been studied, a total of 15 DSW pumping stations are operated in Japan
We found that the DSW of Sagami Bay (Pacific Ocean side of Honshu Island, Japan) contained more unknown actinomycete species than other sea areas, which eventually led to the discovery of akazamicin, a new cytotoxic aromatic polyketide from Nonomuraea [13] and akazaoxime, an antibacterial oxime derivative from Micromonospora [14]

Summary

Introduction

Actinomycetes are a valuable source of bioactive compounds, accounting for approximately two thirds of all known antibiotics, and more than 70% of them are produced by the genusStreptomyces [1]. The extract was subjected to silica gel and ODS column chromatography, and the final purification was achieved by reversed-phase HPLC to yield two new spirotetronate polyketides, nomimicins B (1) and C (2), along with a known compound, nomimicin A (4) [15]. From the extract of the fermentation broth cultured in A11M medium, an additional new tetronate polyketide, nomimicin D (3), was isolated (Figure 1).

Results

Conclusion