Advances in synthetic biology of oleaginous yeast Yarrowia lipolytica
for producing non-native chemicals
Eko Roy Marella
Received: 16 April 2018 /Revised: 13 May 2018 /Accepted: 15 May 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Oleaginous yeast Yarrowia lipolytica is an important industrial host for the production of enzymes, oils, fragrances, surfac-
tants, cosmetics, and pharmaceuticals. More recently, improved synthetic biology tools have allowed more extensive
engineering of this yeast species, which lead to the production of non-native metabolites. In this review, we summarize
the recent advances of genome editing tools for Y. lipolytica, including the application of CRISPR/Cas9 system and discuss
case studies, where Y. lipolytica was engineered to produce various non-native chemicals: short-chain fatty alcohols and
alkanes as biofuels, polyunsaturated fatty acids for nutritional and pharmaceutical applications, polyhydroxyalkanoates and
dicarboxylic acids as precursors for biodegradable plastics, carotenoid-type pigments for food and feed, and campesterol as a
precursor for steroid drugs.
Keywords Yarrowia lipolytica
Yarrowia lipolytica is rapidly gaining popularity as an indus-
trial host for production of recombinant proteins and other
chemicals (Darvishi et al. 2017;Madzak2015). This oleagi-
nous yeast species has an exceptional ability to accumulate
lipids and to utilize hydrophobic compounds such as fats,
oil, fatty acids, and n-alkanes (Mafakher et al. 2010;
Mirbagheri et al. 2012). It is generally regarded as safe
(GRAS) by the Food and Drug Administration in the USA.
Native strains of Y. lipolytica are used for the production of
citric acid (Pfizer Inc. and ADM, USA), lipase (Artechno,
Belgium), erythritol (Baolingbao Biology Co., China), fodder
yeast, and probiotics (Skotan SA, Poland). British Petroleum
(UK) produced single-cell proteins from this yeast for live-
stock feeding (Toprina G) until 1978 (Groenewald et al.
2014;DarvishiHarzevili2014). Furthermore, genetically
engineered strains of Y. lipolytica are used for the production
of eicosapentaenoic acid (EPA)-rich single-cell oils (DuPont,
USA), human lysosomal enzymes for the treatment of lyso-
somal storage diseases (Oxyrane, Belgium and UK), and li-
pase for the treatment of exocrine pancreatic insufficiency
(Mayoly Spindler, France) as enzyme replacement therapies
(Sibirny et al. 2014).
Moreover, native strains of Y. lipolytica are applied for the
bioremediation of environments contaminated with aliphatic
and aromatic compounds, organic pollutants, 2,4,6-trinitrotol-
uene, and metals (Darvishi Harzevili 2014). The freeze-dried
Y. lipolytica cells and extracellular lipases are produced by
Artechno (Belgium) for bioremediation of oily wastewaters
(Darvishi et al. 2012).
Therefore, this non-conventional oleaginous yeast is a valu-
able candidate for industrial and environmental applications.
The genomes of several strains of Y. lipolytica have been
sequenced and are publicly available from NCBI or GRYC
databases (http://igenolevures.org/). The genome of Y.
lipolytica type strain CLIB99 size is ca. 20.5 Mb with a GC
content of 49% which is organized in six chromosomes
* Farshad Darvishi
* Irina Borodina
Microbial Biotechnology and Bioprocess Engineering (MBBE)
Group, Department of Microbiology, Faculty of Science, University
of Maragheh, Maragheh 55181-83111, Iran
The Novo Nordisk Foundation Center for Biosustainability,
Technical University of Denmark, Kemitorvet 220, 2800 Kgs.
Applied Microbiology and Biotechnology