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Bioactive Natural Compounds: Biology and Chemistry

Burnside D, Moteshareie M, Galvan-Marquez I, Hooshyar M, Samanfar B, Shostak K, Omidi K, Peery H, Smith ML, and Golshani A: Use of chemical genomics to investigate the mechanism of action for inhibitory bioactive natural compounds. In G. Brahmachari (Ed.), Bioactive Natural Compounds: Biology and Chemistry. Wiley-VCH publication, 2015, 544 pages. ISBN: 978-3-527-33794-1.

Abstract

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 offer a stepping stone to 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 combinatorial haploinsufficiency/homozygous mutant profiling (HIP/HOP) as genomic tools to investigate MOA in naturally derived inhibitory compounds.

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