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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00747

Multi-omics analysis of fatty alcohol production in engineered yeasts Saccharomyces cerevisiae and Yarrowia lipolytica

 Jonathan Dahlin1, Carina Holkenbrink1, Eko R. Marella1, Guokun Wang1,  Ulf Liebal2,  Christian Lieven1, Dieter Weber2, Douglas McCloskey1,  BIrgitta E. Ebert2,  Markus J. Herrgard1,  Lars M. Blank2 and  Irina Borodina1*
  • 1The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain), Denmark
  • 2Institute of Applied Microbiology, RWTH Aachen University, Germany

Fatty alcohols are widely used in various applications within a diverse set of industries, such as the soap and detergent industry, the personal care and cosmetics industry, as well as the food industry. The total world production of fatty alcohols is over 2 million tons with approximately equal parts derived from fossil oil and from plant oils or animal fats. Due to the environmental impact of these production methods, there is an interest in alternative methods for fatty alcohol production via microbial fermentation using cheap renewable feedstocks.
In this study, we aimed to obtain a better understanding of how fatty alcohol biosynthesis impacts the host organism, baker’s yeast Saccharomyces cerevisiae or oleaginous yeast Yarrowia lipolytica. Producing and non-producing strains were compared in growth and nitrogen-depletion cultivation phases. The multi-omics analysis included physiological characterization, transcriptome analysis by RNAseq, 13C metabolic flux analysis, and intracellular metabolomics.
Both species accumulated fatty alcohols under nitrogen-depletion conditions but not during growth. The fatty alcohol-producing Y. lipolytica strain had a higher fatty alcohol production rate than an analogous S. cerevisiae strain. Nitrogen-depletion phase was associated with lower glucose uptake rates and a decrease in the intracellular concentration of acetyl-CoA in both yeast species, as well as increased organic acid secretion rates in Y. lipolytica. Expression of the fatty-alcohol producing enzyme fatty acyl-CoA reductase alleviated the growth defect caused by deletion of hexadecenal dehydrogenase encoding genes (HFD1 and HFD4) in Y. lipolytica. RNAseq analysis showed that fatty alcohol production triggered a cell wall stress response in S. cerevisiae. RNAseq analysis also showed that both nitrogen-depletion and fatty alcohol production have substantial effects on the expression of transporter encoding genes in Y. lipolytica.
In conclusion, through this multi-omics study, we uncovered some effects of fatty alcohol production on the host metabolism. This knowledge can be used as guidance for further strain improvement towards the production of fatty alcohols.

Keywords: fatty alcohol, Metabolome, 13C-fluxome, Transcriptome, yarrowia lipolytica, Saccharomyces cerevisiae

Received: 15 Apr 2019; Accepted: 17 Jul 2019.

Copyright: © 2019 Dahlin, Holkenbrink, Marella, Wang, Liebal, Lieven, Weber, McCloskey, Ebert, Herrgard, Blank and Borodina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Irina Borodina, The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain), Kgs. Lyngby, Denmark, irbo@biosustain.dtu.dk