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

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

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.756962

DOI=10.3389/fchem.2021.756962

ISSN=2296-2646

ABSTRACT=<p>Angucyclines and angucyclinones represent the largest family of type II PKS-engineered natural products. Chemical analysis of a marine <italic>Streptomyces</italic> 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 (<italic>R</italic><sub><italic>a</italic></sub>)- and (<italic>S</italic><sub><italic>a</italic></sub>)-actetrophenol B (3) bear an unprecedented <italic>N</italic>-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 <italic>Staphylococcus aureus</italic> and <italic>Enterococcus faecium</italic> with MIC values of 4 μg/ml, in contrast, the positive control antimicrobial agent penicillin was inactive up to 32 μg/ml.</p>