Pentacyclic antibiotics from a tidal mud flat-derived actinomycete

Area of Science:

• Natural Product Chemistry
• Marine Microbiology
• Medicinal Chemistry

Background:

• Marine actinomycetes, particularly Streptomyces species, are prolific sources of diverse secondary metabolites with significant biological activities.
• The exploration of unique ecological niches, such as tidal mudflats, can lead to the discovery of novel microorganisms and their chemical products.

Purpose of the Study:

• To isolate and characterize new secondary metabolites from a marine Streptomyces strain.
• To evaluate the biological activities, including cytotoxicity and antimicrobial effects, of the discovered compounds.

Main Methods:

• LC/MS-based screening was employed for bacterial strain selection.
• 1D and 2D NMR spectroscopy, including (13)C-(13)C COSY, and X-ray crystallography were used for structural elucidation of buanmycin.
• (13)C-labeling with (13)C-glucose was performed to determine the carbon backbone.
• Marfey's method was applied to establish the absolute configuration.
• NMR and MS data were utilized for buanquinone structure determination.

Main Results:

• Two new secondary metabolites, buanmycin (a pentacyclic xanthone) and buanquinone (a pentacyclic quinone), were discovered.
• Buanmycin demonstrated potent cytotoxicity against colorectal (HCT-116) and gastric (SNU-638) carcinoma cells (submicromolar IC50).
• Buanmycin exhibited strong inhibition against Salmonella enterica (MIC = 0.7 μM) and showed inhibitory activity against sortase A.

Conclusions:

• The marine Streptomyces strain from Buan, Republic of Korea, is a source of novel bioactive compounds.
• Buanmycin possesses significant anticancer and antibacterial properties, with potential as a lead compound for drug discovery.
• Inhibition of sortase A by buanmycin highlights its potential as a novel antibiotic agent targeting Gram-negative bacteria.