title: Pentacyclic antibiotics from a tidal mud flat-derived actinomycete.
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.
authors.affiliation: †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Kyuho
authors.initials: K
authors.lastname: Moon
authors.affiliation: ‡Department of Agricultural Biotechnology, College of Agriculture and Life Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
authors.forename: Beomkoo
authors.initials: B
authors.lastname: Chung
authors.affiliation: †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Shin
authors.affiliation: §Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States.
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Rheingold
authors.affiliation: §Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States.
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Moore
authors.affiliation: ⊥College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Sung Jean
authors.initials: SJ
authors.lastname: Park
authors.affiliation: †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Sunghyouk
authors.initials: S
authors.lastname: Park
authors.affiliation: †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.affiliation: ‡Department of Agricultural Biotechnology, College of Agriculture and Life Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Oh
authors.affiliation: †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.affiliation: †Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Dong-Chan
authors.initials: DC
authors.lastname: Oh
mesh_terms: D039903:Actinobacteria / Q000737:chemistry*; D019881:Aminoacyltransferases / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D056910:Republic of Korea; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D011809:Quinones; C000598677:buanmycin; C000598678:buanquinone; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases