title: Glionitrin A, an antibiotic-antitumor metabolite derived from competitive interaction between abandoned mine microbes.
abstract: The nutrient conditions present in abandoned coal mine drainages create an extreme environment where defensive and offensive microbial interactions could be critical for survival and fitness. Coculture of a mine drainage-derived Sphingomonas bacterial strain, KMK-001, and a mine drainage-derived Aspergillus fumigatus fungal strain, KMC-901, resulted in isolation of a new diketopiperazine disulfide, glionitrin A (1). Compound 1 was not detected in monoculture broths of KMK-001 or KMC-901. The structure of 1, a (3S,10aS) diketopiperazine disulfide containing a nitro aromatic ring, was based on analysis of MS, NMR, and circular dichroism spectra and confirmed by X-ray crystal data. Glionitrin A displayed significant antibiotic activity against a series of microbes including methicillin-resistant Staphylococcus aureus. An in vitro MTT cytotoxicity assay revealed that 1 had potent submicromolar cytotoxic activity against four human cancer cell lines: HCT-116, A549, AGS, and DU145. The results provide further evidence that microbial coculture can produce novel biologically relevant molecules.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 210-340, Republic of Korea.
authors.forename: Hyun Bong
authors.initials: HB
authors.lastname: Park
authors.forename: Hak Cheol
authors.initials: HC
authors.lastname: Kwon
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001230:Aspergillus / Q000737:chemistry / Q000378:metabolism*; D003032:Coal Mining; D018360:Crystallography, X-Ray; D054659:Diketopiperazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008968:Molecular Conformation; D015394:Molecular Structure; D020578:Sphingomonas / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D054659:Diketopiperazines; C550392:glionitrin A