Seipke, RF and Hutchings, MI (2013) The regulation and biosynthesis of antimycins. Beilstein Journal of Organic Chemistry, 9. 2556 - 2563. ISSN 1860-5397
Abstract
Antimycins (>40 members) were discovered nearly 65 years ago but the discovery of the gene cluster encoding antimycin biosynthesis in 2011 has facilitated rapid progress in understanding the unusual biosynthetic pathway. Antimycin A is widely used as a piscicide in the catfish farming industry and also has potent killing activity against insects, nematodes and fungi. The mode of action of antimycins is to inhibit cytochrome c reductase in the electron transport chain and halt respiration. However, more recently, antimycin A has attracted attention as a potent and selective inhibitor of the mitochondrial anti-apoptotic proteins Bcl-2 and Bcl-xL. Remarkably, this inhibition is independent of the main mode of action of antimycins such that an artificial derivative named 2-methoxyantimycin A inhibits Bcl-xL but does not inhibit respiration. The Bcl-2/Bcl-xL family of proteins are overproduced in cancer cells that are resistant to apoptosis-inducing chemotherapy agents, so antimycins have great potential as anticancer drugs used in combination with existing chemotherapeutics. Here we review what is known about antimycins, the regulation of the ant gene cluster and the unusual biosynthetic pathway.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 Seipke and Hutchings; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution CC BY 2.0 License |
Keywords: | antimycins; gene regulation; genome mining; natural products; Streptomyces |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Aug 2014 13:56 |
Last Modified: | 17 Aug 2015 13:36 |
Published Version: | http://dx.doi.org/10.3762/bjoc.9.290 |
Status: | Published |
Publisher: | Beilstein-Institut |
Identification Number: | 10.3762/bjoc.9.290 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:80026 |