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Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway
Antibiotic biosynthetic gene clusters (BGCs) produce bioactive metabolites that impart a fitness advantage to their producer, providing a mechanism for natural selection. This selection drives antibiotic evolution and adapts BGCs for expression in different organisms, potentially providing clues to...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443133/ https://www.ncbi.nlm.nih.gov/pubmed/32826900 http://dx.doi.org/10.1038/s41467-020-18018-2 |
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author | Johnston, Chad W. Badran, Ahmed H. Collins, James J. |
author_facet | Johnston, Chad W. Badran, Ahmed H. Collins, James J. |
author_sort | Johnston, Chad W. |
collection | PubMed |
description | Antibiotic biosynthetic gene clusters (BGCs) produce bioactive metabolites that impart a fitness advantage to their producer, providing a mechanism for natural selection. This selection drives antibiotic evolution and adapts BGCs for expression in different organisms, potentially providing clues to improve heterologous expression of antibiotics. Here, we use phage-assisted continuous evolution (PACE) to achieve bioactivity-dependent adaptation of the BGC for the antibiotic bicyclomycin (BCM), facilitating improved production in a heterologous host. This proof-of-principle study demonstrates that features of natural bioactivity-dependent evolution can be engineered to access unforeseen routes of improving metabolic pathways and product yields. |
format | Online Article Text |
id | pubmed-7443133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74431332020-09-02 Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway Johnston, Chad W. Badran, Ahmed H. Collins, James J. Nat Commun Article Antibiotic biosynthetic gene clusters (BGCs) produce bioactive metabolites that impart a fitness advantage to their producer, providing a mechanism for natural selection. This selection drives antibiotic evolution and adapts BGCs for expression in different organisms, potentially providing clues to improve heterologous expression of antibiotics. Here, we use phage-assisted continuous evolution (PACE) to achieve bioactivity-dependent adaptation of the BGC for the antibiotic bicyclomycin (BCM), facilitating improved production in a heterologous host. This proof-of-principle study demonstrates that features of natural bioactivity-dependent evolution can be engineered to access unforeseen routes of improving metabolic pathways and product yields. Nature Publishing Group UK 2020-08-21 /pmc/articles/PMC7443133/ /pubmed/32826900 http://dx.doi.org/10.1038/s41467-020-18018-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Johnston, Chad W. Badran, Ahmed H. Collins, James J. Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
title | Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
title_full | Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
title_fullStr | Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
title_full_unstemmed | Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
title_short | Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
title_sort | continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443133/ https://www.ncbi.nlm.nih.gov/pubmed/32826900 http://dx.doi.org/10.1038/s41467-020-18018-2 |
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