Surveying the lipogenesis landscape in Yarrowia lipolytica through understanding the function of a Mga2p regulatory protein mutant

Metab Eng. 2015 Sep:31:102-11. doi: 10.1016/j.ymben.2015.07.004. Epub 2015 Jul 26.

Abstract

Lipogenic organisms represent great starting points for metabolic engineering of oleochemical production. While previous engineering efforts were able to significantly improve lipid production in Yarrowia lipolytica, the lipogenesis landscape, especially with respect to regulatory elements, has not been fully explored. Through a comparative genomics and transcriptomics approach, we identified and validated a mutant mga2 protein that serves as a regulator of desaturase gene expression and potent lipogenesis factor. The resulting strain is enriched in unsaturated fatty acids. Comparing the underlying mechanism of this mutant to other previously engineered strains suggests that creating an imbalance between glycolysis and the TCA cycle can serve as a driving force for lipogenesis when combined with fatty acid catabolism overexpressions. Further comparative transcriptomics analysis revealed both distinct and convergent rewiring associated with these different genotypes. Finally, by combining metabolic engineering targets, it is possible to further engineer a strain containing the mutant mga2 gene to a lipid production titer of 25g/L.

Keywords: Lipogenesis; Metabolic engineering; Yarrowia; Yeast; mga2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fatty Acid Desaturases / genetics*
  • Fatty Acids, Unsaturated / analysis
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Gene Expression Regulation, Enzymologic
  • Lipogenesis*
  • Metabolic Engineering
  • Mutant Proteins / physiology*
  • Polymorphism, Single Nucleotide
  • Transcriptome
  • Yarrowia / genetics
  • Yarrowia / metabolism*

Substances

  • Fatty Acids, Unsaturated
  • Fungal Proteins
  • Mutant Proteins
  • Fatty Acid Desaturases