Pentacyclic Antibiotics from a Tidal Mud Flat-Derived Actinomycete

The combination of investigating
a unique source of chemically
prolific bacterium with an LC/MS-based bacterial strain selection
approach resulted in the discovery of two new secondary metabolites,
buanmycin (1) and buanquinone (2), from
the culture of a marine Streptomyces strain, which
was isolated from a tidal mudflat in Buan, Republic of Korea. The
carbon backbone of buanmycin (1), comprising 20 quaternary
carbons out of 30 total carbons, was determined via 13C–13C COSY NMR analysis after labeling 1 with 13C by culturing the bacterium with 13C-glucose.
The complete structure of 1 was confidently elucidated,
primarily based on 1D and 2D NMR spectroscopic and X-ray crystallographic
analysis, as that of a new pentacyclic xanthone. The absolute configuration
of the α-methyl serine unit in 1 was established
by applying the advanced Marfey’s method. The structure of
buanquinone (2) was determined to be a new pentacyclic
quinone based on NMR and MS spectroscopic data. Buanmycin exhibited
potent cytotoxicity against colorectal carcinoma cells (HCT-116) and
gastric carcinoma cells (SNU-638) with submicromolar IC50 values and strongly inhibited the pathogenic Gram-negative bacterium Salmonella enterica (MIC = 0.7 μM). In particular,
buanmycin demonstrated inhibition of sortase A, which is a promising
target for antibiotic discovery.