Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production
Journal article, 2020
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.
Omics
Metabolic Engineering
Systems Biology
Author
Snorre Sulheim
Norwegian University of Science and Technology (NTNU)
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Tjaša Kumelj
Norwegian University of Science and Technology (NTNU)
Dino van Dissel
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Ali Salehzadeh-Yazdi
University of Rostock
Chao Du
Leiden University
Gilles P. van Wezel
Leiden University
Kay Nieselt
University of Tübingen
Eivind Almaas
Norwegian University of Science and Technology (NTNU)
Alexander Wentzel
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Eduard Kerkhoven
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Novo Nordisk Foundation
iScience
25890042 (eISSN)
Vol. 23 9 101525Subject Categories
Biochemistry and Molecular Biology
Bioprocess Technology
Microbiology
Bioinformatics (Computational Biology)
Bioinformatics and Systems Biology
DOI
10.1016/j.isci.2020.101525