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Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters

Microbial natural products (NPs) are a major source of pharmacological agents. Most NPs are synthesized from specific biosynthetic gene clusters (BGCs). With the rapid increase of sequenced microbial genomes, large numbers of NP BGCs have been discovered, regarded as a treasure trove of novel bioact...

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Autores principales: Wang, Wenfang, Zheng, Guosong, Lu, Yinhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314000/
https://www.ncbi.nlm.nih.gov/pubmed/34327194
http://dx.doi.org/10.3389/fbioe.2021.692797
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author Wang, Wenfang
Zheng, Guosong
Lu, Yinhua
author_facet Wang, Wenfang
Zheng, Guosong
Lu, Yinhua
author_sort Wang, Wenfang
collection PubMed
description Microbial natural products (NPs) are a major source of pharmacological agents. Most NPs are synthesized from specific biosynthetic gene clusters (BGCs). With the rapid increase of sequenced microbial genomes, large numbers of NP BGCs have been discovered, regarded as a treasure trove of novel bioactive compounds. However, many NP BGCs are silent in native hosts under laboratory conditions. In order to explore their therapeutic potential, a main route is to activate these silent NP BGCs in heterologous hosts. To this end, the first step is to accurately and efficiently capture these BGCs. In the past decades, a large number of effective technologies for cloning NP BGCs have been established, which has greatly promoted drug discovery research. Herein, we describe recent advances in strategies for BGC cloning, with a focus on the preparation of high-molecular-weight DNA fragment, selection and optimization of vectors used for carrying large-size DNA, and methods for assembling targeted DNA fragment and appropriate vector. The future direction into novel, universal, and high-efficiency methods for cloning NP BGCs is also prospected.
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spelling pubmed-83140002021-07-28 Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters Wang, Wenfang Zheng, Guosong Lu, Yinhua Front Bioeng Biotechnol Bioengineering and Biotechnology Microbial natural products (NPs) are a major source of pharmacological agents. Most NPs are synthesized from specific biosynthetic gene clusters (BGCs). With the rapid increase of sequenced microbial genomes, large numbers of NP BGCs have been discovered, regarded as a treasure trove of novel bioactive compounds. However, many NP BGCs are silent in native hosts under laboratory conditions. In order to explore their therapeutic potential, a main route is to activate these silent NP BGCs in heterologous hosts. To this end, the first step is to accurately and efficiently capture these BGCs. In the past decades, a large number of effective technologies for cloning NP BGCs have been established, which has greatly promoted drug discovery research. Herein, we describe recent advances in strategies for BGC cloning, with a focus on the preparation of high-molecular-weight DNA fragment, selection and optimization of vectors used for carrying large-size DNA, and methods for assembling targeted DNA fragment and appropriate vector. The future direction into novel, universal, and high-efficiency methods for cloning NP BGCs is also prospected. Frontiers Media S.A. 2021-07-13 /pmc/articles/PMC8314000/ /pubmed/34327194 http://dx.doi.org/10.3389/fbioe.2021.692797 Text en Copyright © 2021 Wang, Zheng and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Wang, Wenfang
Zheng, Guosong
Lu, Yinhua
Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
title Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
title_full Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
title_fullStr Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
title_full_unstemmed Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
title_short Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
title_sort recent advances in strategies for the cloning of natural product biosynthetic gene clusters
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314000/
https://www.ncbi.nlm.nih.gov/pubmed/34327194
http://dx.doi.org/10.3389/fbioe.2021.692797
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