Pentacyclic antibiotics from a tidal mud flat-derived actinomycete

  • J Nat Prod. 2015 Mar 27;78(3):524-9. doi: 10.1021/np500736b.
Kyuho Moon  1 ,  Beomkoo Chung  2 ,  Yoonho Shin  1 ,  Arnold L Rheingold  3 ,  Curtis E Moore  3 ,  Sung Jean Park  4 ,  Sunghyouk Park  1 ,  Sang Kook Lee  1 ,  Ki-Bong Oh  2 ,  Jongheon Shin  1 ,  Dong-Chan Oh  1
Affiliations
  • 1. †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
  • 2. ‡Department of Agricultural Biotechnology, College of Agriculture and Life Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
  • 3. §Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States.
  • 4. ⊥College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.
PMID: 25495422 DOI: 10.1021/np500736b
Abstract

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 (13)C-(13)C COSY NMR analysis after labeling 1 with (13)C by culturing the bacterium with (13)C-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.