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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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Autores principales: Seipke, Ryan F, Hutchings, Matthew I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869250/
https://www.ncbi.nlm.nih.gov/pubmed/24367419
http://dx.doi.org/10.3762/bjoc.9.290
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author Seipke, Ryan F
Hutchings, Matthew I
author_facet Seipke, Ryan F
Hutchings, Matthew I
author_sort Seipke, Ryan F
collection PubMed
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-x(L). Remarkably, this inhibition is independent of the main mode of action of antimycins such that an artificial derivative named 2-methoxyantimycin A inhibits Bcl-x(L) but does not inhibit respiration. The Bcl-2/Bcl-x(L) 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.
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spelling pubmed-38692502013-12-23 The regulation and biosynthesis of antimycins Seipke, Ryan F Hutchings, Matthew I Beilstein J Org Chem Review 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-x(L). Remarkably, this inhibition is independent of the main mode of action of antimycins such that an artificial derivative named 2-methoxyantimycin A inhibits Bcl-x(L) but does not inhibit respiration. The Bcl-2/Bcl-x(L) 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. Beilstein-Institut 2013-11-19 /pmc/articles/PMC3869250/ /pubmed/24367419 http://dx.doi.org/10.3762/bjoc.9.290 Text en Copyright © 2013, Seipke and Hutchings https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Review
Seipke, Ryan F
Hutchings, Matthew I
The regulation and biosynthesis of antimycins
title 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_short The regulation and biosynthesis of antimycins
title_sort regulation and biosynthesis of antimycins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869250/
https://www.ncbi.nlm.nih.gov/pubmed/24367419
http://dx.doi.org/10.3762/bjoc.9.290
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