Neo-actinomycins A and B, natural actinomycins bearing the 5H-oxazolo[4,5-b]phenoxazine chromophore, from the marine-derived Streptomyces sp. IMB094

Qiang Wang,Yiguang Wang,Hongwei He,Maoluo Gan,Mian Wang,Chunling Xiao,Yixuan Zhang,Xuefu You,Xinxin Hu,Yi Tan

doi:10.1038/s41598-017-03769-8

Abstract

Neo-actinomycins A and B (1 and 2), two new natural actinomycins featuring an unprecedented tetracyclic 5H-oxazolo[4,5-b]phenoxazine chromophore, were isolated from the marine-derived actinomycete Streptomyces sp. IMB094. Their structures were elucidated by spectroscopic analyses. The presence of this ring system was proposed to originate from a condensation between actinomycin D (3) with α-ketoglutarate and pyruvate, respectively. Compound 1 showed potent cytotoxic activities against human cancer HCT116 and A549 cell lines in the nanomolar range (IC50: 38.7 and 65.8 nM, respectively) and moderate antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) strains.

Highlights

Actinomycins are well-known chromopeptides with potent cytotoxic and antibiotic activities, isolated from various Actinomyces strains[1] and consisting of a tricyclic phenoxazinone chromophore attached to two pentapeptide lactone rings via amide bonds
IMB094 isolated from marine sediment showed potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA) (MIC of
The chromophore of neo-actinomycin A (1) contains a fourth oxazole ring fused with the actinocin moiety, forming a tetracyclic 5H-oxazolo[4,5-b]phenoxazine ring, which has never previously been found in naturally occurring actinomycins

Summary

Introduction

Actinomycins are well-known chromopeptides with potent cytotoxic and antibiotic activities, isolated from various Actinomyces strains[1] and consisting of a tricyclic phenoxazinone chromophore attached to two pentapeptide lactone rings via amide bonds. Extensive analysis of 2D NMR (HSQC, COSY, and HMBC) spectroscopic data revealed 10 amino acid residues in 1: 2 × Thr, 2 × Val, 2 × Pro, 2 × sarcosin (Sar), 2 × MeVal. Amino acid sequences in the two peptidolactone units in 1 were determined to be identical with those of actinomycin D using HMBC correlations (Fig. 2).

Results

Conclusion