Abstract
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, 13Cmetabolic 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.
Highlights
Fatty alcohols are used as detergents and surfactants in personal care products such as soaps, shampoos, or creams
13C-flux analysis revealed fundamentally different metabolic profiles of the two yeast species S. cerevisiae and Y. lipolytica (Figure 5), which is in line with previous findings (Christen and Sauer, 2011)
For S. cerevisiae, this means that removal of ethanol production and increased NADPH generation are necessary
Summary
Fatty alcohols are used as detergents and surfactants in personal care products such as soaps, shampoos, or creams. Escherichia coli was engineered to produce 6.3 g/L total fatty alcohols (Liu et al, 2016) (bioreactor, complex media). Yarrowia lipolytica has been engineered to produce 2.2 g/L (Xu et al, 2016) (bioreactor, minimal media), and Lipomyces starkeyi was engineered to produce 1.7 g/L (McNeil and Stuart 2018) (shake flask, minimal media). To this date, the highest reported titer of 8 g/L total alcohols was obtained with oleaginous yeast Rhodosporidium toruloides (Fillet et al, 2015) (bioreactor, complex media)
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