Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production
Artikel i vetenskaplig tidskrift, 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
Författare
Snorre Sulheim
Norges teknisk-naturvitenskapelige universitet
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Tjaša Kumelj
Norges teknisk-naturvitenskapelige universitet
Dino van Dissel
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Ali Salehzadeh-Yazdi
Universität Rostock
Chao Du
Universiteit Leiden
Gilles P. van Wezel
Universiteit Leiden
Kay Nieselt
Universität Tübingen
Eivind Almaas
Norges teknisk-naturvitenskapelige universitet
Alexander Wentzel
Sintef Foundation for Scientific and Industrial Research At the Norwegian Institute of Technology
Eduard Kerkhoven
Chalmers, Biologi och bioteknik, Systembiologi
Novo Nordisk Fonden
iScience
25890042 (eISSN)
Vol. 23 9 101525Ämneskategorier
Biokemi och molekylärbiologi
Bioprocessteknik
Mikrobiologi
Bioinformatik (beräkningsbiologi)
Bioinformatik och systembiologi
DOI
10.1016/j.isci.2020.101525