Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production
Summary: Many biosynthetic gene clusters (BGCs) require heterologous expression to realize their genetic potential, including silent and metagenomic BGCs. Although the engineered Streptomyces coelicolor M1152 is a widely used host for heterologous expression of BGCs, a systemic understanding of how...
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doaj-f41af98888e14fc2be2e920391988f962020-11-25T01:38:26ZengElsevieriScience2589-00422020-09-01239101525Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous ProductionSnorre Sulheim0Tjaša Kumelj1Dino van Dissel2Ali Salehzadeh-Yazdi3Chao Du4Gilles P. van Wezel5Kay Nieselt6Eivind Almaas7Alexander Wentzel8Eduard J. Kerkhoven9Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway; Department of Biotechnology and Food Science, NTNU - Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Biotechnology and Food Science, NTNU - Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, NorwayDepartment of Systems Biology and Bioinformatics, Faculty of Computer Science and Electrical Engineering, University of Rostock, 18057 Rostock, GermanyMicrobial Biotechnology, Institute of Biology, Leiden University, 2300 Leiden, the NetherlandsMicrobial Biotechnology, Institute of Biology, Leiden University, 2300 Leiden, the NetherlandsIntegrative Transcriptomics, Center for Bioinformatics, University of Tübingen, 72070 Tübingen, GermanyDepartment of Biotechnology and Food Science, NTNU - Norwegian University of Science and Technology, 7491 Trondheim, Norway; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and General Practice, NTNU - Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, NorwaySystems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Corresponding authorSummary: Many biosynthetic gene clusters (BGCs) require heterologous expression to realize their genetic potential, including silent and metagenomic BGCs. Although the engineered Streptomyces coelicolor M1152 is a widely used host for heterologous expression of BGCs, a systemic understanding of how its genetic modifications affect the metabolism is lacking and limiting further development. We performed a comparative analysis of M1152 and its ancestor M145, connecting information from proteomics, transcriptomics, and cultivation data into a comprehensive picture of the metabolic differences between these strains. Instrumental to this comparison was the application of an improved consensus genome-scale metabolic model (GEM) of S. coelicolor. Although many metabolic patterns are retained in M1152, we find that this strain suffers from oxidative stress, possibly caused by increased oxidative metabolism. Furthermore, precursor availability is likely not limiting polyketide production, implying that other strategies could be beneficial for further development of S. coelicolor for heterologous production of novel compounds.http://www.sciencedirect.com/science/article/pii/S2589004220307173Systems BiologyOmicsMetabolic Engineering |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Snorre Sulheim Tjaša Kumelj Dino van Dissel Ali Salehzadeh-Yazdi Chao Du Gilles P. van Wezel Kay Nieselt Eivind Almaas Alexander Wentzel Eduard J. Kerkhoven |
spellingShingle |
Snorre Sulheim Tjaša Kumelj Dino van Dissel Ali Salehzadeh-Yazdi Chao Du Gilles P. van Wezel Kay Nieselt Eivind Almaas Alexander Wentzel Eduard J. Kerkhoven Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production iScience Systems Biology Omics Metabolic Engineering |
author_facet |
Snorre Sulheim Tjaša Kumelj Dino van Dissel Ali Salehzadeh-Yazdi Chao Du Gilles P. van Wezel Kay Nieselt Eivind Almaas Alexander Wentzel Eduard J. Kerkhoven |
author_sort |
Snorre Sulheim |
title |
Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production |
title_short |
Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production |
title_full |
Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production |
title_fullStr |
Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production |
title_full_unstemmed |
Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production |
title_sort |
enzyme-constrained models and omics analysis of streptomyces coelicolor reveal metabolic changes that enhance heterologous production |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2020-09-01 |
description |
Summary: Many biosynthetic gene clusters (BGCs) require heterologous expression to realize their genetic potential, including silent and metagenomic BGCs. Although the engineered Streptomyces coelicolor M1152 is a widely used host for heterologous expression of BGCs, a systemic understanding of how its genetic modifications affect the metabolism is lacking and limiting further development. We performed a comparative analysis of M1152 and its ancestor M145, connecting information from proteomics, transcriptomics, and cultivation data into a comprehensive picture of the metabolic differences between these strains. Instrumental to this comparison was the application of an improved consensus genome-scale metabolic model (GEM) of S. coelicolor. Although many metabolic patterns are retained in M1152, we find that this strain suffers from oxidative stress, possibly caused by increased oxidative metabolism. Furthermore, precursor availability is likely not limiting polyketide production, implying that other strategies could be beneficial for further development of S. coelicolor for heterologous production of novel compounds. |
topic |
Systems Biology Omics Metabolic Engineering |
url |
http://www.sciencedirect.com/science/article/pii/S2589004220307173 |
work_keys_str_mv |
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