Informatic analysis reveals Legionella as a source of novel natural products
Microbial natural products are a crucial source of bioactive molecules and unique chemical scaffolds. Despite their importance, rediscovery of known natural products from established productive microbes has led to declining interest, even while emergent genomic data suggest that the majority of micr...
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doaj-c5bf22687abd41b08871f2b55b0829342021-02-02T07:31:57ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2016-06-011213013610.1016/j.synbio.2015.12.001Informatic analysis reveals Legionella as a source of novel natural productsChad W. Johnston0Jonathan Plumb1Xiang Li2Sergio Grinstein3Nathan A. Magarvey4The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5Microbial natural products are a crucial source of bioactive molecules and unique chemical scaffolds. Despite their importance, rediscovery of known natural products from established productive microbes has led to declining interest, even while emergent genomic data suggest that the majority of microbial natural products remain to be discovered. Now, new sources of microbial natural products must be defined in order to provide chemical scaffolds for the next generation of small molecules for therapeutic, agricultural, and industrial purposes. In this work, we use specialized bioinformatic programs, genetic knockouts, and comparative metabolomics to define the genus Legionella as a new source of novel natural products. We show that Legionella spp. hold a diverse collection of biosynthetic gene clusters for the production of polyketide and nonribosomal peptide natural products. To confirm this bioinformatic survey, we create targeted mutants of L. pneumophila and use comparative metabolomics to identify a novel polyketide surfactant. Using spectroscopic techniques, we show that this polyketide possesses a new chemical scaffold, and firmly demonstrate that this unexplored genus is a source for novel natural products.http://www.sciencedirect.com/science/article/pii/S2405805X15300193Natural productsLegionellaPolyketidesPRISM |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chad W. Johnston Jonathan Plumb Xiang Li Sergio Grinstein Nathan A. Magarvey |
spellingShingle |
Chad W. Johnston Jonathan Plumb Xiang Li Sergio Grinstein Nathan A. Magarvey Informatic analysis reveals Legionella as a source of novel natural products Synthetic and Systems Biotechnology Natural products Legionella Polyketides PRISM |
author_facet |
Chad W. Johnston Jonathan Plumb Xiang Li Sergio Grinstein Nathan A. Magarvey |
author_sort |
Chad W. Johnston |
title |
Informatic analysis reveals Legionella as a source of novel natural products |
title_short |
Informatic analysis reveals Legionella as a source of novel natural products |
title_full |
Informatic analysis reveals Legionella as a source of novel natural products |
title_fullStr |
Informatic analysis reveals Legionella as a source of novel natural products |
title_full_unstemmed |
Informatic analysis reveals Legionella as a source of novel natural products |
title_sort |
informatic analysis reveals legionella as a source of novel natural products |
publisher |
KeAi Communications Co., Ltd. |
series |
Synthetic and Systems Biotechnology |
issn |
2405-805X |
publishDate |
2016-06-01 |
description |
Microbial natural products are a crucial source of bioactive molecules and unique chemical scaffolds. Despite their importance, rediscovery of known natural products from established productive microbes has led to declining interest, even while emergent genomic data suggest that the majority of microbial natural products remain to be discovered. Now, new sources of microbial natural products must be defined in order to provide chemical scaffolds for the next generation of small molecules for therapeutic, agricultural, and industrial purposes. In this work, we use specialized bioinformatic programs, genetic knockouts, and comparative metabolomics to define the genus Legionella as a new source of novel natural products. We show that Legionella spp. hold a diverse collection of biosynthetic gene clusters for the production of polyketide and nonribosomal peptide natural products. To confirm this bioinformatic survey, we create targeted mutants of L. pneumophila and use comparative metabolomics to identify a novel polyketide surfactant. Using spectroscopic techniques, we show that this polyketide possesses a new chemical scaffold, and firmly demonstrate that this unexplored genus is a source for novel natural products. |
topic |
Natural products Legionella Polyketides PRISM |
url |
http://www.sciencedirect.com/science/article/pii/S2405805X15300193 |
work_keys_str_mv |
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