The regulation and biosynthesis of antimycins
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 an...
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doaj-0e793138eb1347e7926428a903931db82021-02-02T07:50:15ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972013-11-01912556256310.3762/bjoc.9.2901860-5397-9-290The regulation and biosynthesis of antimycinsRyan F. Seipke0Matthew I. Hutchings1School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, United KingdomSchool of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, United KingdomAntimycins (>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 over-produced 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.https://doi.org/10.3762/bjoc.9.290antimycinsgene regulationgenome miningnatural productsStreptomyces |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ryan F. Seipke Matthew I. Hutchings |
spellingShingle |
Ryan F. Seipke Matthew I. Hutchings The regulation and biosynthesis of antimycins Beilstein Journal of Organic Chemistry antimycins gene regulation genome mining natural products Streptomyces |
author_facet |
Ryan F. Seipke Matthew I. Hutchings |
author_sort |
Ryan F. Seipke |
title |
The regulation and biosynthesis of antimycins |
title_short |
The regulation and biosynthesis of antimycins |
title_full |
The regulation and biosynthesis of antimycins |
title_fullStr |
The regulation and biosynthesis of antimycins |
title_full_unstemmed |
The regulation and biosynthesis of antimycins |
title_sort |
regulation and biosynthesis of antimycins |
publisher |
Beilstein-Institut |
series |
Beilstein Journal of Organic Chemistry |
issn |
1860-5397 |
publishDate |
2013-11-01 |
description |
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 over-produced 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. |
topic |
antimycins gene regulation genome mining natural products Streptomyces |
url |
https://doi.org/10.3762/bjoc.9.290 |
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