Tunicamycins from Marine-Derived <i>Streptomyces bacillaris</i> Inhibit MurNAc-Pentapeptide Translocase in <i>Staphylococcus aureus</i>
Jayho Lee,
Ji-Yeon Hwang,
Daehyun Oh,
Dong-Chan Oh,
Hyeung-geun Park,
Jongheon Shin,
Ki-Bong Oh
Affiliations
Jayho Lee
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea
Ji-Yeon Hwang
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Daehyun Oh
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Dong-Chan Oh
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Hyeung-geun Park
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Jongheon Shin
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Ki-Bong Oh
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea
Four tunicamycin class compounds, tunicamycin VII (1), tunicamycin VIII (2), corynetoxin U17a (3), and tunicamycin IX (4), were isolated from the culture broth of the marine-derived actinomycete Streptomyces sp. MBTG32. The strain was identified using the 16S rDNA sequencing technique, and the isolated strain was closely related to Streptomyces bacillaris. The structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported NMR data. Compounds 1–4 showed potent antibacterial activities against Gram-positive bacteria, especially Staphylococcus aureus, with MIC values of 0.13–0.25 µg/mL. Through a recombinant enzyme assay and overexpression analysis, we found that the isolated compounds exerted potent inhibitory effects on S. aureus MurNAc-pentapeptide translocase (MraY), with IC50 values of 0.08–0.21 µg/mL. The present results support that the underlying mechanism of action of tunicamycins isolated from marine-derived Streptomyces sp. is also associated with the inhibition of MraY enzyme activity in S. aureus.
