Ring D-Modified and Highly Reduced Angucyclinones From Marine Sediment-Derived Streptomyces sp.

Lin Guo,Xiaohong Pan,Shumin Zhang,Zeping Xie,Gennaro Pescitelli,Ming Liu,Guangfei Wang,Qiaoli Yang

doi:10.3389/fchem.2021.756962

Lin Guo, Xiaohong Pan + Show 6 more

Open Access

https://doi.org/10.3389/fchem.2021.756962

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Abstract

Angucyclines and angucyclinones represent the largest family of type II PKS-engineered natural products. Chemical analysis of a marine Streptomyces sp. KCB-132 yielded three new members, actetrophenone A (1) and actetrophenols A–B (2–3). Their structures were elucidated by NMR spectroscopy, X-ray crystallography and CD calculations. Actetrophenone A (1) is the first representative of a novel-type angucyclinone bearing a nonaromatic D-ring. Actetrophenol A (2) features a highly reduced and aromatized four-ring system, which is unprecedented for natural products. While (R a )- and (S a )-actetrophenol B (3) bear an unprecedented N-acetyltryptamine-substituted tetraphene core skeleton, this is the first report of a pair of atropisomeric isomers in the angucyclinone family. Actetrophenol A (2) exhibits remarkable antibiotic activity, notably including potent activity to multiple resistant Staphylococcus aureus and Enterococcus faecium with MIC values of 4 μg/ml, in contrast, the positive control antimicrobial agent penicillin was inactive up to 32 μg/ml.

Highlights

Angucyclines and angucyclinones, characterized by an unsymmetrically assembled benz[a] anthraquinone frame, represent by far the largest family of type II PKS-engineered natural products (Kharel et al, 2012)
As part of our research on the discovery of new-type angucyclinones from marine sedimentderived bacteria, we reported several angucyclinones featuring C-ring cleavage and expansion, produced by Streptomyces pratensis KCB-132 (Zhang et al, 2017; Zhang et al, 2019)
Actetrophenol A (2) featured a highly conjugated and aromatized tetraphene ring system, which is unprecedented for natural products

Summary

INTRODUCTION

Angucyclines and angucyclinones, characterized by an unsymmetrically assembled benz[a] anthraquinone frame, represent by far the largest family of type II PKS-engineered natural products (Kharel et al, 2012). This family of antibiotics has attracted much attention due to their broad biological activities and remarkable structural diversity that is mainly derived from oxidation, hydroxylation and glycosylation at various positions (Bringmann et al, 2005; Shaaban et al, 2012; Xie et al, 2016), and rearrangement of A-, B- and C-ring (Ma et al, 2015; Liu et al, 2019; Wu et al, 2019).

RESULTS AND DISCUSSION

CONCLUSION

DATA AVAILABILITY STATEMENT