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Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster
Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of them have not been characterized. Here we apply a plug and play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969335/ https://www.ncbi.nlm.nih.gov/pubmed/24305602 http://dx.doi.org/10.1038/ncomms3894 |
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author | Luo, Yunzi Huang, Hua Liang, Jing Wang, Meng Lu, Lu Shao, Zengyi Cobb, Ryan E. Zhao, Huimin |
author_facet | Luo, Yunzi Huang, Hua Liang, Jing Wang, Meng Lu, Lu Shao, Zengyi Cobb, Ryan E. Zhao, Huimin |
author_sort | Luo, Yunzi |
collection | PubMed |
description | Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of them have not been characterized. Here we apply a plug and play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from Streptomyces griseus and discover three potential PTMs. This gene cluster is highly conserved in phylogenetically diverse bacterial strains and contains an unusual hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) which resembles iterative PKSs known in fungi. To further characterize this gene cluster, we use the same synthetic biology approach to create a series of gene deletion constructs and elucidate the biosynthetic steps for the formation of the polycyclic system. The strategy we employ bypasses the traditional laborious processes to elicit gene cluster expression and should be generally applicable to many other silent or cryptic gene clusters for discovery and characterization of new natural products. |
format | Online Article Text |
id | pubmed-3969335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39693352014-03-28 Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster Luo, Yunzi Huang, Hua Liang, Jing Wang, Meng Lu, Lu Shao, Zengyi Cobb, Ryan E. Zhao, Huimin Nat Commun Article Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of them have not been characterized. Here we apply a plug and play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from Streptomyces griseus and discover three potential PTMs. This gene cluster is highly conserved in phylogenetically diverse bacterial strains and contains an unusual hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) which resembles iterative PKSs known in fungi. To further characterize this gene cluster, we use the same synthetic biology approach to create a series of gene deletion constructs and elucidate the biosynthetic steps for the formation of the polycyclic system. The strategy we employ bypasses the traditional laborious processes to elicit gene cluster expression and should be generally applicable to many other silent or cryptic gene clusters for discovery and characterization of new natural products. 2013 /pmc/articles/PMC3969335/ /pubmed/24305602 http://dx.doi.org/10.1038/ncomms3894 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Luo, Yunzi Huang, Hua Liang, Jing Wang, Meng Lu, Lu Shao, Zengyi Cobb, Ryan E. Zhao, Huimin Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster |
title | Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster |
title_full | Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster |
title_fullStr | Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster |
title_full_unstemmed | Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster |
title_short | Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster |
title_sort | activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969335/ https://www.ncbi.nlm.nih.gov/pubmed/24305602 http://dx.doi.org/10.1038/ncomms3894 |
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