Unravelling evolutionary strategies of yeast for improving galactose utilization through integrated systems level analysis
Journal article, 2011

Identification of the underlying molecular mechanisms for a derived phenotype by adaptive evolution is difficult. Here, we performed a systems-level inquiry into the metabolic changes occurring in the yeast Saccharomyces cerevisiae as a result of its adaptive evolution to increase its specific growth rate on galactose and related these changes to the acquired phenotypic properties. Three evolved mutants (62A, 62B, and 62C) with higher specific growth rates and faster specific galactose uptake were isolated. The evolved mutants were compared with a reference strain and two engineered strains, SO16 and PGM2, which also showed higher galactose uptake rate in previous studies. The profile of intermediates in galactose metabolism was similar in evolved and engineered mutants, whereas reserve carbohydrates metabolism was specifically elevated in the evolved mutants and one evolved strain showed changes in ergosterol biosynthesis. Mutations were identified in proteins involved in the global carbon sensing Ras/PKA pathway, which is known to regulate the reserve carbohydrates metabolism. We evaluated one of the identified mutations, RAS2(Tyr112), and this mutation resulted in an increased specific growth rate on galactose. These results show that adaptive evolution results in the utilization of unpredicted routes to accommodate increased galactose flux in contrast to rationally engineered strains. Our study demonstrates that adaptive evolution represents a valuable alternative to rational design in bioengineering of improved strains and, that through systems biology, it is possible to identify mutations in evolved strain that can serve as unforeseen metabolic engineering targets for improving microbial strains for production of biofuels and chemicals.

saccharomyces-cerevisiae

industrial

metabolism

network

escherichia-coli

phosphoglucomutase

stress tolerance

strains

glucose

Author

Kuk-ki Hong

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Wanwipa Vongsangnak

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Goutham Vemuri

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 108 29 12179-12184

Industrial Systems Biology of Yeast and A. oryzae (INSYSBIO)

European Commission (FP7), 2010-01-01 -- 2014-12-31.

Roots

Basic sciences

Areas of Advance

Life Science Engineering (2010-2018)

Subject Categories

Chemical Sciences

DOI

10.1073/pnas.1103219108

More information

Created

10/8/2017