Glionitrin A, an antibiotic-antitumor metabolite derived from competitive interaction between abandoned mine microbes.
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.
Park
Hyun Bong
HB
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 210-340, Republic of Korea.
Kwon
Hak Cheol
HC
Lee
Chang-Ho
CH
Yang
Hyun Ok
HO
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*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D054659:Diketopiperazines; C550392:glionitrin A