Comparison of the metabolic response to over-production of p-coumaric acid in two yeast strains
Artikel i vetenskaplig tidskrift, 2017

The development of robust and efficient cell factories requires understanding of the metabolic changes triggered by the production of the targeted compound. Here we aimed to study how production of p-coumaric acid, a precursor of multiple secondary aromatic metabolites, influences the cellular metabolism of Saccharomyces cerevisiae. We evaluated the growth and p-coumaric acid production in batch and chemostat cultivations and analyzed the transcriptome and intracellular metabolome during steady state in low-and high-producers of p-coumaric acid in two strain backgrounds, S288c or CEN.PK. We found that the same genetic modifications resulted in higher production of p-coumaric acid in the CEN.PK background than in the S288c background. Moreover, the CEN.PK strain was less affected by the genetic engineering as was evident from fewer changes in the transcription profile and intracellular metabolites concentrations. Surprisingly, for both strains we found the largest transcriptional changes in genes involved in transport of amino acids and sugars, which were downregulated. Additionally, in S288c amino acid and protein biosynthesis processes were also affected. We systematically overexpressed or deleted genes with significant transcriptional changes in CEN.PK low and high-producing strains. The knockout of some of the downregulated transporters triggered a 20-50% improvement in the synthesis of p-CA in the CEN.PK high-producing strain. This study demonstrates the importance of transporters in the engineering of cell factories for production of small molecules.

Transporters

p-Coumaric acid

engineered saccharomyces-cerevisiae

escherichia-coli

Metabolome data

p569

1994

tolerance

eels el

Transcriptome

Saccharomyces cerevisiae

microbiology-uk

v140

integration

gene-set analysis

Biotechnology & Applied Microbiology

oxidative stress

expression

osmoregulation

ethanol

network topology

Författare

A. Rodriguez

Technische Universiteit Delft

Danmarks Tekniske Universitet (DTU)

Yun Chen

Chalmers, Biologi och bioteknik, Systembiologi

Sakda Khoomrung

Chalmers, Biologi och bioteknik, Systembiologi

E. Ozdemir

Danmarks Tekniske Universitet (DTU)

I. Borodina

Danmarks Tekniske Universitet (DTU)

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 44 265-272

Styrkeområden

Building Futures

Livsvetenskaper och teknik

Ämneskategorier

Biokemi och molekylärbiologi

Biologiska vetenskaper

DOI

10.1016/j.ymben.2017.10.013

Mer information

Senast uppdaterat

2018-05-14