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Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii

Streptomyces leeuwenhoekii, isolated from the hyperarid Atacama Desert, produces the new ansamycin-like compounds chaxamycins A to D, which possess potent antibacterial activity and moderate antiproliferative activity. We report the development of genetic tools to manipulate S. leeuwenhoekii and the...

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Detalles Bibliográficos
Autores principales: Castro, Jean Franco, Razmilic, Valeria, Gomez-Escribano, Juan Pablo, Andrews, Barbara, Asenjo, Juan A., Bibb, Mervyn J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551226/
https://www.ncbi.nlm.nih.gov/pubmed/26092459
http://dx.doi.org/10.1128/AEM.01039-15
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author Castro, Jean Franco
Razmilic, Valeria
Gomez-Escribano, Juan Pablo
Andrews, Barbara
Asenjo, Juan A.
Bibb, Mervyn J.
author_facet Castro, Jean Franco
Razmilic, Valeria
Gomez-Escribano, Juan Pablo
Andrews, Barbara
Asenjo, Juan A.
Bibb, Mervyn J.
author_sort Castro, Jean Franco
collection PubMed
description Streptomyces leeuwenhoekii, isolated from the hyperarid Atacama Desert, produces the new ansamycin-like compounds chaxamycins A to D, which possess potent antibacterial activity and moderate antiproliferative activity. We report the development of genetic tools to manipulate S. leeuwenhoekii and the identification and partial characterization of the 80.2-kb chaxamycin biosynthesis gene cluster, which was achieved by both mutational analysis in the natural producer and heterologous expression in Streptomyces coelicolor A3(2) strain M1152. Restoration of chaxamycin production in a nonproducing ΔcxmK mutant (cxmK encodes 3-amino-5-hydroxybenzoic acid [AHBA] synthase) was achieved by supplementing the growth medium with AHBA, suggesting that mutasynthesis may be a viable approach for the generation of novel chaxamycin derivatives.
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spelling pubmed-45512262015-09-22 Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii Castro, Jean Franco Razmilic, Valeria Gomez-Escribano, Juan Pablo Andrews, Barbara Asenjo, Juan A. Bibb, Mervyn J. Appl Environ Microbiol Genetics and Molecular Biology Streptomyces leeuwenhoekii, isolated from the hyperarid Atacama Desert, produces the new ansamycin-like compounds chaxamycins A to D, which possess potent antibacterial activity and moderate antiproliferative activity. We report the development of genetic tools to manipulate S. leeuwenhoekii and the identification and partial characterization of the 80.2-kb chaxamycin biosynthesis gene cluster, which was achieved by both mutational analysis in the natural producer and heterologous expression in Streptomyces coelicolor A3(2) strain M1152. Restoration of chaxamycin production in a nonproducing ΔcxmK mutant (cxmK encodes 3-amino-5-hydroxybenzoic acid [AHBA] synthase) was achieved by supplementing the growth medium with AHBA, suggesting that mutasynthesis may be a viable approach for the generation of novel chaxamycin derivatives. American Society for Microbiology 2015-08-07 2015-09 /pmc/articles/PMC4551226/ /pubmed/26092459 http://dx.doi.org/10.1128/AEM.01039-15 Text en Copyright © 2015, Castro et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Genetics and Molecular Biology
Castro, Jean Franco
Razmilic, Valeria
Gomez-Escribano, Juan Pablo
Andrews, Barbara
Asenjo, Juan A.
Bibb, Mervyn J.
Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii
title Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii
title_full Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii
title_fullStr Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii
title_full_unstemmed Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii
title_short Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii
title_sort identification and heterologous expression of the chaxamycin biosynthesis gene cluster from streptomyces leeuwenhoekii
topic Genetics and Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551226/
https://www.ncbi.nlm.nih.gov/pubmed/26092459
http://dx.doi.org/10.1128/AEM.01039-15
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