Microbiology news and views
J. Mol. Micro. Biotechnol. 3: 301-308
Expression and Isolation of Antimicrobial Small Molecules from Soil DNA Libraries
I.A. MacNeil, C. L. Tiong, C. Minor, P.R. August, T.H. Grossman, K.A. Loiacono, B.A. Lynch, T. Phillips, S. Narula, R. Sundaramoorthi,
A. Tyler, T. Aldredge, H. Long, M. Gilman, D. Holt, and M.S. Osburne
Natural products have been a critically important source of clinically relevant small molecule
therapeutics. However, the discovery rate of novel structural classes of antimicrobial molecules has declined.
Recently, increasing evidence has shown that the number of species cultivated from soil represents less than 1% of
the total population, opening up the exciting possibility that these uncultured species may provide a large
untapped pool from which novel natural products can be discovered. We have constructed and expressed in
E. coli a BAC (bacterial artificial chromosome) library containing genomic fragments of DNA (5-120kb) isolated
directly from soil organisms (S-DNA). Screening of the library resulted in the identification of several
antimicrobial activities expressed by different recombinant clones. One clone (mg1.1) has been partially characterized
and found to express several small molecules related to and including indirubin. These results show that
genes involved in natural product synthesis can be cloned directly from S-DNA and expressed in a heterologous
host, supporting the idea that this technology has the potential to provide novel natural products from the wealth
of environmental microbial diversity and is a potentially important new tool for drug discovery.
Full article [pdf]
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