Use of chemical genomics to investigate the mechanism of action for inhibitory bioactive natural compounds
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.
|Keywords||Chemical genetic profiling, Gene deletion array, Haploinsufficiency mutant profiling, Homozygous mutant profiling, Mechanism of action, Natural inhibitory compounds|
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