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

Systems Biology

Metabolic Engineering

Author

Snorre Sulheim

Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology

Norwegian University of Science and Technology (NTNU)

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

Eduard J. Kerkhoven

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Novo Nordisk Foundation Center for Biosustainability

iScience

25890042 (eISSN)

Vol. 23 9 101525

Subject Categories

Bioprocess Technology

Microbiology

Bioinformatics and Systems Biology

DOI

10.1016/j.isci.2020.101525

More information

Latest update

10/29/2020