Issue 5, 2016

Strategies for target identification of antimicrobial natural products

Abstract

Covering: 2000 to 2015

Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

Graphical abstract: Strategies for target identification of antimicrobial natural products

Article information

Article type
Review Article
Submitted
13 ต.ค. 2558
First published
25 ม.ค. 2559

Nat. Prod. Rep., 2016,33, 668-680

Author version available

Strategies for target identification of antimicrobial natural products

M. A. Farha and E. D. Brown, Nat. Prod. Rep., 2016, 33, 668 DOI: 10.1039/C5NP00127G

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