[Identification of tetracenomycin X from a marine-derived Saccharothrix sp. guided by genes sequence analysis].
The crude extracts of the fermentation broth from a marine sediment-derived actinomycete strain, Saccharothrix sp. 10-10, showed significant antibacterial activities against drug-resistant pathogens. A genome-mining PCR-based experiment targeting the genes encoding key enzymes involved in the biosynthesis of secondary metabolites indicated that the strain 10-10 showed the potential to produce tetracenomycin-like compounds. Further chemical investigation of the cultures of this strain led to the identification of two antibiotics, including a tetracenomycin (Tcm) analogs, Tcm X (1), and a tomaymycin derivative, oxotomaymycin (2). Their structures were identified by spectroscopic data analysis, including UV, 1D-NMR, 2D-NMR and MS spectra. Tcm X (1) showed moderate antibacterial activities against a number of drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) pathogens, with the MIC values in the range of 32-64 microg x mL(-1). In addition, 1 also displayed significant cytotoxic activities against human cancer cell lines, including HL60 (leukemia), HepG2 (liver), and MCF-7 (breast) with the IC 50 values of 5.1, 9.7 and 18.0 micromol x L(-1), respectively. Guided by the PCR-based gene sequence analysis, Tcm X (1) and oxotomaymycin (2) were identified from the genus of Saccharothrix and their 13C NMR data were correctly assigned on the basis of 2D NMR spectroscopic data analysis for the first time.
Bin
B
Liu
Yi
Y
Tan
Mao-Luo
ML
Gan
Hong-Xia
HX
Zhou
Yi-Guang
YG
Wang
Yu-Hui
YH
Ping
Bin
B
Li
Zhao-Yong
ZY
Yang
Chun-Ling
CL
Xiao
D000192:Actinomycetales / Q000737:chemistry* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001570:Benzodiazepinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D057225:Data Mining / Q000379:methods; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects; D005285:Fermentation; D023281:Genomics; D006801:Humans; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009279:Naphthacenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010802:Phylogeny; D013212:Staphylococcus epidermidis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D009279:Naphthacenes; C059963:tetracenomycin X; C013184:oxotomaymycin