Discovery of Brominated Alboflavusins With Anti-MRSA Activities

Chao Li; Wuyundalai Bao; Haoyue Zhang; Zhitang Lyu; Yihua Chen; Zhengyan Guo

doi:10.3389/fmicb.2021.641025

Discovery of Brominated Alboflavusins With Anti-MRSA Activities

Front Microbiol. 2021 Feb 16:12:641025. doi: 10.3389/fmicb.2021.641025. eCollection 2021.

Authors

Chao Li^{1

2}, Wuyundalai Bao³, Haoyue Zhang⁴, Zhitang Lyu⁴, Yihua Chen^{1

2}, Zhengyan Guo^{1

2}

Affiliations

¹ State Key Laboratory of Microbial Resources, CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
² College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
³ College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot, China.
⁴ Key Laboratory of Microbial Diversity Research and Application of Hebei Province, Institute of Life Science and Green Development, College of Life Sciences, Hebei University, Baoding, China.

Abstract

As methicillin-resistant Staphylococcus aureus (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 1 and 2) were isolated from the wild-type strain Streptomyces alboflavus sp. 313 that was fermented in the production medium supplemented with NaBr; two new (compounds 3 and 5) and a known (compound 4) dehelogenated AFN congeners were isolated from S. alboflavus ΔafnX, in which the tryptophan halogenase gene afnX 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 1 and 2 with bromine displayed effective activities against the tested MRSA strains. Especially, compound 2 showed good anti-MRSA activity, while compounds 3, 4, and 5 without halogen exhibited weak anti-MRSA activities, outlining the influence of halogen substitution to the bioactivities of AFNs.

Keywords: Alboflavusins; MRSA; antibacterial activity; bromination; structural elucidation.