Bioactive Natural Compounds: Biology and Chemistry
Citation
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.
Plain language summary
One of the most important challenges in developing new drugs is to understand their specific mechanism(s) of action (MOA). Natural products offer a nearly uncountable pool of potential scaffolds for new drugs and have been a primary source for drug development. Genome-scale assays provide a realistic option 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 book chapter discusses the use of genome-wide single deletion arrays (GDAs) in S. cerevisiae and E.coli as genomic tools to investigate MOA in naturally-derived inhibitory compounds
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.