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

Systems Biology

Metabolic Engineering

Författare

Snorre Sulheim

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

Norges teknisk-naturvitenskapelige universitet

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

Eduard J. Kerkhoven

Chalmers, Biologi och bioteknik, Systembiologi

Novo Nordisk Foundation Center for Biosustainability

iScience

25890042 (eISSN)

Vol. 23 9 101525

Ämneskategorier

Bioprocessteknik

Mikrobiologi

Bioinformatik och systembiologi

DOI

10.1016/j.isci.2020.101525

Mer information

Senast uppdaterat

2020-10-29