Issue 7, 2017

Targeting a cell wall biosynthesis hot spot

Abstract

Covering: up to 2017

History points to the bacterial cell wall biosynthetic network as a very effective target for antibiotic intervention, and numerous natural product inhibitors have been discovered. In addition to the inhibition of enzymes involved in the multistep synthesis of the macromolecular layer, in particular, interference with membrane-bound substrates and intermediates essential for the biosynthetic reactions has proven a valuable antibacterial strategy. A prominent target within the peptidoglycan biosynthetic pathway is lipid II, which represents a particular “Achilles' heel” for antibiotic attack, as it is readily accessible on the outside of the cytoplasmic membrane. Lipid II is a unique non-protein target that is one of the structurally most conserved molecules in bacterial cells. Notably, lipid II is more than just a target molecule, since sequestration of the cell wall precursor may be combined with additional antibiotic activities, such as the disruption of membrane integrity or disintegration of membrane-bound multi-enzyme machineries. Within the membrane bilayer lipid II is likely organized in specific anionic phospholipid patches that form a particular “landing platform” for antibiotics. Nature has invented a variety of different “lipid II binders” of at least 5 chemical classes, and their antibiotic activities can vary substantially depending on the compounds' physicochemical properties, such as amphiphilicity and charge, and thus trigger diverse cellular effects that are decisive for antibiotic activity.

Graphical abstract: Targeting a cell wall biosynthesis hot spot

Article information

Article type
Review Article
Submitted
10 फरवरी 2017
First published
04 जुलाई 2017

Nat. Prod. Rep., 2017,34, 909-932

Targeting a cell wall biosynthesis hot spot

A. Müller, A. Klöckner and T. Schneider, Nat. Prod. Rep., 2017, 34, 909 DOI: 10.1039/C7NP00012J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements