One of the most significant hurdles in developing new drugs to treat diseases is understanding the specific mechanism(s) of action (MOA) by which small molecules discovered in cell-based screening exhibit their bioactivity. Natural products offer a nearly innumerable library of potential scaffolds for new drugs and have been a primary source for drug development. The process of characterizing the activity of natural products can be daunting. Traditional pathway-specific mechanistic approaches are time consuming and expensive. Genome scale assays provide a feasible alternative which offers a stepping stone in understanding an antimicrobial's mechanism of action by identifying pathways and genes/proteins whose endogenous activity is affected by the presence of an inhibitory natural compound. This chapter will discuss the use of genome-wide single-deletion arrays (GDAs) in Saccharomyces cerevisiae and Escherichia coli as well as combinatorial haploinsufficiency/homozygous mutant profiling (HIP/HOP) as genomic tools to investigate MOA in naturally derived inhibitory compounds.

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Keywords Chemical genetic profiling, Gene deletion array, Haploinsufficiency mutant profiling, Homozygous mutant profiling, Mechanism of action, Natural inhibitory compounds
Persistent URL dx.doi.org/10.1002/9783527684403.ch2
Citation
Burnside, D. (Daniel), Moteshareie, H. (Houman), Marquez, I.G. (Imelda G.), Hooshyar, M. (Mohsen), Samanfar, B. (Bahram), Shostak, K. (Kristina), … Golshani, A. (2015). Use of chemical genomics to investigate the mechanism of action for inhibitory bioactive natural compounds. In Bioactive Natural Products: Chemistry and Biology (pp. 9–32). doi:10.1002/9783527684403.ch2


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