A systems-level approach for metabolic engineering of yeast cell factories
Artikel i vetenskaplig tidskrift, 2012

The generation of novel yeast cell factories for production of high-value industrial biotechnological products relies on three metabolic engineering principles: design, construction, and analysis. In the last two decades, strong efforts have been put on developing faster and more efficient strategies and/or technologies for each one of these principles. For design and construction, three major strategies are described in this review: (1) rational metabolic engineering; (2) inverse metabolic engineering; and (3) evolutionary strategies. Independent of the selected strategy, the process of designing yeast strains involves five decision points: (1) choice of product, (2) choice of chassis, (3) identification of target genes, (4) regulating the expression level of target genes, and (5) network balancing of the target genes. At the construction level, several molecular biology tools have been developed through the concept of synthetic biology and applied for the generation of novel, engineered yeast strains. For comprehensive and quantitative analysis of constructed strains, systems biology tools are commonly used and using a multi-omics approach. Key information about the biological system can be revealed, for example, identification of genetic regulatory mechanisms and competitive pathways, thereby assisting the in silico design of metabolic engineering strategies for improving strain performance. Examples on how systems and synthetic biology brought yeast metabolic engineering closer to industrial biotechnology are described in this review, and these examples should demonstrate the potential of a systems-level approach for fast and efficient generation of yeast cell factories.

omics'

gene-expression

ribosome entry site

fermentation

glucose repression

xylose

in silico strain optimization

synthetic biology

ethanol-production

in-vivo kinetics

synthetic biology

Saccharomyces cerevisiae

functional genomics

metabolic engineering

technologies

systems biology

directed evolution

saccharomyces-cerevisiae strains

Författare

Il-Kwon Kim

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Antonio Roldao

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Verena Siewers

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Jens B Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

FEMS Yeast Research

1567-1356 (ISSN) 1567-1364 (eISSN)

Vol. 12 2 228-248

Ämneskategorier

Industriell bioteknik

Styrkeområden

Energi

Livsvetenskaper och teknik

DOI

10.1111/j.1567-1364.2011.00779.x