AUTHOR=Li Chao , Bao Wuyundalai , Zhang Haoyue , Lyu Zhitang , Chen Yihua , Guo Zhengyan 

TITLE=Discovery of Brominated Alboflavusins With Anti-MRSA Activities

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.641025

DOI=10.3389/fmicb.2021.641025

ISSN=1664-302X

ABSTRACT=<p>As methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA) is becoming a serious pathogenic threaten to human health worldwide, there is an urgent need to discover new antibiotics for the treatment of MRSA infections. Alboflavusins (AFNs) are a group of halogenated cyclohexapeptides with anti-MRSA activities. In this study, two novel brominated AFN congeners (compounds <bold>1</bold> and <bold>2</bold>) were isolated from the wild-type strain <italic>Streptomyces alboflavus</italic> sp. 313 that was fermented in the production medium supplemented with NaBr; two new (compounds <bold>3</bold> and <bold>5</bold>) and a known (compound <bold>4</bold>) dehelogenated AFN congeners were isolated from <italic>S. alboflavus</italic> Δ<italic>afnX</italic>, in which the tryptophan halogenase gene <italic>afnX</italic> was inactivated. The structures of these compounds were assigned by careful NMR and MS analyses. The anti-MRSA activities of varied AFN congeners were assessed against different MRSA strains, which revealed that compounds <bold>1</bold> and <bold>2</bold> with bromine displayed effective activities against the tested MRSA strains. Especially, compound <bold>2</bold> showed good anti-MRSA activity, while compounds <bold>3</bold>, <bold>4</bold>, and <bold>5</bold> without halogen exhibited weak anti-MRSA activities, outlining the influence of halogen substitution to the bioactivities of AFNs.</p>