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Metabolic engineering of Saccharomyces cerevisiae for the overproduction of short branched-chain fatty acids
- Source :
- Metabolic Engineering. 34:36-43
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Short branched-chain fatty acids (SBCFAs, C4-6) are versatile platform intermediates for the production of value-added products in the chemical industry. Currently, SBCFAs are mainly synthesized chemically, which can be costly and may cause environmental pollution. In order to develop an economical and environmentally friendly route for SBCFA production, we engineered Saccharomyces cerevisiae, a model eukaryotic microorganism of industrial significance, for the overproduction of SBCFAs. In particular, we employed a combinatorial metabolic engineering approach to optimize the native Ehrlich pathway in S. cerevisiae. First, chromosome-based combinatorial gene overexpression led to a 28.7-fold increase in the titer of SBCFAs. Second, deletion of key genes in competing pathways improved the production of SBCFAs to 387.4 mg/L, a 31.2-fold increase compared to the wild-type. Third, overexpression of the ATP-binding cassette (ABC) transporter PDR12 increased the secretion of SBCFAs. Taken together, we demonstrated that the combinatorial metabolic engineering approach used in this study effectively improved SBCFA biosynthesis in S. cerevisiae through the incorporation of a chromosome-based combinatorial gene overexpression strategy, elimination of genes in competitive pathways and overexpression of a native transporter. We envision that this strategy could also be applied to the production of other chemicals in S. cerevisiae and may be extended to other microbes for strain improvement.
- Subjects :
- 0106 biological sciences
0301 basic medicine
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae
Environmental pollution
Bioengineering
01 natural sciences
Applied Microbiology and Biotechnology
Metabolic engineering
03 medical and health sciences
chemistry.chemical_compound
Biosynthesis
010608 biotechnology
Metabolome
Overproduction
Gene
biology
Fatty Acids
Transporter
biology.organism_classification
Recombinant Proteins
Up-Regulation
Genetic Enhancement
030104 developmental biology
Metabolic Engineering
chemistry
Biochemistry
Metabolic Networks and Pathways
Biotechnology
Subjects
Details
- ISSN :
- 10967176
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Metabolic Engineering
- Accession number :
- edsair.doi.dedup.....f3368028b9a96c7032a6473f28cbb4c3
- Full Text :
- https://doi.org/10.1016/j.ymben.2015.12.005