Soil DNA libraries for anticancer drug discovery.
Soil has the largest population of microbes of any habitat, but only about 0.3% of soil microbes are cultivable with current techniques. Cultured soil microbes have been an incredibly productive source of drugs, for example the cancer chemotherapeutics doxorubicin hydrochloride, bleomycin, daunorubicin and mitomycin. Unfortunately, the current yield of new drugs from soil microbes is low due to repeated cultivation of the same small fraction of cultivable microbes. Uncultured soil species represent a tremendous untapped resource of new antineoplastic agents. Methods have recently been developed to access the diversity of secondary metabolites from uncultured soil microbes. Briefly, total DNA is extracted from soil samples, purified, partially digested, and fragments inserted into vectors for expression in readily fermented microbes such as Escherichia coli. Clones expressing enzymatic and antibiotic activities that are encoded by novel sequences have been reported.
Pettit
Robin K
RK
Cancer Research Institute and Department of Microbiology, Arizona State University, Tempe, AZ 85287, USA. pettitr@asu.edu
D000970:Antineoplastic Agents; D022202:Chromosomes, Artificial, Bacterial; D002965:Classification; D004269:DNA, Bacterial / Q000302:isolation & purification*; D004271:DNA, Fungal / Q000302:isolation & purification*; D004354:Drug Screening Assays, Antitumor; D005285:Fermentation; D020869:Gene Expression Profiling; D015723:Gene Library; D006801:Humans; D012988:Soil Microbiology
D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D004271:DNA, Fungal