Abstract
Yarrowia lipolytica is a non-conventional oleaginous yeast with great potential for industrial production. Y. lipolytica has a high propensity for flux through tricarboxylic acid cycle intermediates. Therefore, this host is currently being developed as a workhorse, and is rapidly emerging in biotechnology fields, especially for industrial chemical production, whole-cell bioconversion, and the treatment and recycling of industrial waste. In recent studies, Y. lipolytica has been rewritten and introduced with non-native metabolites of certain compounds of interest owing to the advancement in synthetic biology tools. In this review, we collate recent progress to present a detailed and insightful summary of the major developments in synthetic biology tools and techniques for Y. lipolytica, including promoters, terminators, selection markers, autonomously replicating sequences, DNA assembly techniques, genome editing techniques, and subcellular organelle engineering. This comprehensive overview would be a useful resource for future genetic engineering studies to improve the yield of desired metabolic products in Y. lipolytica.
Similar content being viewed by others
Data availability
This review is a summary of the original data and does not produce any new data.
References
Amalia L, Zhang Y, Ju Y-H, Tsai S-L (2020) Enhanced lipid production in Yarrowia lipolytica Po1g by over-expressing lro1 gene under two different promoters. Appl Biochem Biotechnol 191:104–111. https://doi.org/10.1007/s12010-020-03226-9
An-adirekkun J, Stewart CJ, Geller SH et al (2020) A yeast optogenetic toolkit (yOTK) for gene expression control in Saccharomyces cerevisiae. Biotechnol Bioeng 117:886–893. https://doi.org/10.1002/bit.27234
Bae S-J, Park BG, Kim B-G, Hahn J-S (2020) Multiplex gene disruption by targeted base editing of Yarrowia lipolytica genome using cytidine deaminase combined with the CRISPR/Cas9 system. Biotechnol J 15:e1900238. https://doi.org/10.1002/biot.201900238
Bai Q (2020) Establishment of genomic library technology based on non-homologous end joining mechanism in Yarrowia lipolytica. Sci China Life Sci. https://doi.org/10.1007/s11427-020-1885-x
Bai Q, Cheng S, Zhang J et al (2021) Establishment of genomic library technology mediated by non-homologous end joining mechanism in Yarrowia lipolytica. Sci China Life Sci 64:2114–2128. https://doi.org/10.1007/s11427-020-1885-x
Baisya D, Ramesh A, Schwartz C et al (2022) Genome-wide functional screens enable the prediction of high activity CRISPR-Cas9 and -Cas12a guides in Yarrowia lipolytica. Nat Commun 13:922. https://doi.org/10.1038/s41467-022-28540-0
Bandi CK, Skalenko KS, Agrawal A et al (2021) Engineered regulon to enable autonomous azide ion biosensing, recombinant protein production, and in vivo glycoengineering. ACS Synth Biol 10:682–689. https://doi.org/10.1021/acssynbio.0c00449
Beopoulos A, Verbeke J, Bordes F et al (2014) Metabolic engineering for ricinoleic acid production in the oleaginous yeast Yarrowia lipolytica. Appl Microbiol Biotechnol 98:251–262. https://doi.org/10.1007/s00253-013-5295-x
Bhutada G, Kavšček M, Hofer F et al (2018) Characterization of a lipid droplet protein from Yarrowia lipolytica that is required for its oleaginous phenotype. Biochim Biophys Acta Mol Cell Biol Lipids 1863:1193–1205. https://doi.org/10.1016/j.bbalip.2018.07.010
Blazeck J, Liu L, Redden H, Alper H (2011) Tuning gene expression in Yarrowia lipolytica by a hybrid promoter approach. Appl Environ Microbiol 77:7905–7914. https://doi.org/10.1128/AEM.05763-11
Bredeweg EL, Baker SE (2021) Strain construction for intracellular metabolic pathway localization in Y. lipolytica. Methods Mol Biol 2307:147–157. https://doi.org/10.1007/978-1-0716-1414-3_10
Celińska E, Ledesma-Amaro R, Larroude M et al (2017) Golden gate assembly system dedicated to complex pathway manipulation in Yarrowia lipolytica. Microb Biotechnol 10:450–455. https://doi.org/10.1111/1751-7915.12605
Chattopadhyay A, Mitra M, Maiti MK (2021) Recent advances in lipid metabolic engineering of oleaginous yeasts. Biotechnol Adv 53:107722. https://doi.org/10.1016/j.biotechadv.2021.107722
Chatzivasileiou AO, Ward V, Edgar SM, Stephanopoulos G (2019) Two-step pathway for isoprenoid synthesis. Proc Natl Acad Sci USA 116:506–511. https://doi.org/10.1073/pnas.1812935116
Chen Y, Partow S, Scalcinati G et al (2012) Enhancing the copy number of episomal plasmids in Saccharomyces cerevisiae for improved protein production. FEMS Yeast Res 12:598–607. https://doi.org/10.1111/j.1567-1364.2012.00809.x
Cordero Otero R, Gaillardin C (1996) Efficient selection of hygromycin-B-resistant Yarrowia lipolytica transformants. Appl Microbiol Biotechnol 46:143–148. https://doi.org/10.1007/s002530050796
Cui Z, Zheng H, Zhang J et al (2021) A CRISPR/Cas9-mediated, homology-independent tool developed for targeted genome integration in Yarrowia lipolytica. Appl Environ Microbiol 87:e02666-e2720. https://doi.org/10.1128/AEM.02666-20
Curran KA, Morse NJ, Markham KA et al (2015) Short synthetic terminators for improved heterologous gene expression in yeast. ACS Synth Biol 4:824–832. https://doi.org/10.1021/sb5003357
Damiati S (2019) New opportunities for creating man-made bioarchitectures utilizing microfluidics. Biomed Microdevices 21:62. https://doi.org/10.1007/s10544-019-0415-8
Darvishi F, Ariana M, Marella ER, Borodina I (2018) Advances in synthetic biology of oleaginous yeast Yarrowia lipolytica for producing non-native chemicals. Appl Microbiol Biotechnol 102:5925–5938. https://doi.org/10.1007/s00253-018-9099-x
Diep P, Boucinha A, Kell B et al (2021) Advancing undergraduate synthetic biology education: insights from a Canadian iGEM student perspective. Can J Microbiol 67:749–770. https://doi.org/10.1139/cjm-2020-0549
Edwards H, Yang Z, Xu P (2020) Characterization of Met25 as a color associated genetic marker in Yarrowia lipolytica. Metab Eng 11:e00147. https://doi.org/10.1016/j.mec.2020.e00147
Fatma Z, Schultz JC, Zhao H (2020) Recent advances in domesticating non-model microorganisms. Biotechnol Prog 36:e3008. https://doi.org/10.1002/btpr.3008
Ganesan V, Spagnuolo M, Agrawal A et al (2019) Advances and opportunities in gene editing and gene regulation technology for Yarrowia lipolytica. Microb Cell Fact 18:208. https://doi.org/10.1186/s12934-019-1259-x
Gao S, Han L, Zhu L et al (2014) One-step integration of multiple genes into the oleaginous yeast Yarrowia lipolytica. Biotechnol Lett 36:2523–2528. https://doi.org/10.1007/s10529-014-1634-y
Gao D, Smith S, Spagnuolo M et al (2018) Dual CRISPR-Cas9 cleavage mediated gene excision and targeted integration in Yarrowia lipolytica. Biotechnol J 13:1700590. https://doi.org/10.1002/biot.201700590
Gemperlein K, Dietrich D, Kohlstedt M et al (2019) Polyunsaturated fatty acid production by Yarrowia lipolytica employing designed myxobacterial PUFA synthases. Nat Commun 10:4055. https://doi.org/10.1038/s41467-019-12025-8
Ghogare R, Chen S, Xiong X (2020) Metabolic engineering of oleaginous yeast Yarrowia lipolytica for overproduction of fatty acids. Front Microbiol 11:1717. https://doi.org/10.3389/fmicb.2020.01717
Gibson DG, Young L, Chuang R-Y et al (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6:343–345. https://doi.org/10.1038/nmeth.1318
Giwa AS, Ali N (2022) Perspectives of nervonic acid production by Yarrowia lipolytica. Biotechnol Lett 44:193–202. https://doi.org/10.1007/s10529-022-03231-4
Gu Y, Ma J, Zhu Y, Xu P (2020) Refactoring ehrlich pathway for high-yield 2-phenylethanol production in Yarrowia lipolytica. ACS Synth Biol 9:623–633. https://doi.org/10.1021/acssynbio.9b00468
Guo Y, Dong J, Zhou T et al (2015) YeastFab: the design and construction of standard biological parts for metabolic engineering in Saccharomyces cerevisiae. Nucleic Acids Res 43:e88–e88. https://doi.org/10.1093/nar/gkv464
Guo Q, Shi T, Peng Q et al (2021) Harnessing Yarrowia lipolytica peroxisomes as a subcellular factory for α-humulene overproduction. J Agric Food Chem 69:13831–13837. https://doi.org/10.1021/acs.jafc.1c05897
Guo Q, Li Y, Yan F et al (2022) Dual cytoplasmic-peroxisomal engineering for high-yield production of sesquiterpene α-humulene in Yarrowia lipolytica. Biotechnol Bioeng. https://doi.org/10.1002/bit.28176
Haldimann A, Wanner BL (2001) Conditional-replication, integration, excision, and retrieval plasmid-host systems for gene structure-function studies of bacteria. J Bacteriol 183:6384–6393. https://doi.org/10.1128/JB.183.21.6384-6393.2001
Hamilton M, Consiglio AL, MacEwen K et al (2020) Identification of a Yarrowia lipolytica acetamidase and its use as a yeast genetic marker. Microb Cell Fact 19:22. https://doi.org/10.1186/s12934-020-1292-9
Hanko EKR, Denby CM, Sanchez I Nogue V et al (2018) Engineering β-oxidation in Yarrowia lipolytica for methyl ketone production. Metab Eng 48:52–62. https://doi.org/10.1016/j.ymben.2018.05.018
He YJ, Meghani K, Caron M-C et al (2018) DYNLL1 binds MRE11 to limit DNA end resection in BRCA1-deficient cells. Nature 563:522–526. https://doi.org/10.1038/s41586-018-0670-5
Holkenbrink C, Dam MI, Kildegaard KR et al (2018) EasyCloneYALI: CRISPR/Cas9-based synthetic toolbox for engineering of the yeast Yarrowia lipolytica. Biotechnol J 13:1700543. https://doi.org/10.1002/biot.201700543
Hu C, Wu S, Wang Q et al (2011) Simultaneous utilization of glucose and xylose for lipid production by Trichosporon cutaneum. Biotechnol Biofuels 4:25. https://doi.org/10.1186/1754-6834-4-25
Imatoukene N, Back A, Nonus M et al (2020) Fermentation process for producing CFAs using Yarrowia lipolytica. J Ind Microbiol Biotechnol 47:403–412. https://doi.org/10.1007/s10295-020-02276-6
Jain A, Bhatia P, Chugh A (2012) Microbial synthetic biology for human therapeutics. Syst Synth Biol 6:9–22. https://doi.org/10.1007/s11693-012-9092-0
Jang I-S, Yu BJ, Jang JY et al (2018) Improving the efficiency of homologous recombination by chemical and biological approaches in Yarrowia lipolytica. PLoS ONE 13:e0194954. https://doi.org/10.1371/journal.pone.0194954
Jiang Z, Cui Z, Zhu Z et al (2021) Engineering of Yarrowia lipolytica transporters for high-efficient production of biobased succinic acid from glucose. Biotechnol Biofuels 14:145. https://doi.org/10.1186/s13068-021-01996-w
Jinek M, Chylinski K, Fonfara I et al (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821. https://doi.org/10.1126/science.1225829
Kamineni A, Chen S, Chifamba G, Tsakraklides V (2020) Promoters for lipogenesis-specific downregulation in Yarrowia lipolytica. FEMS Yeast Res 20:foaa035. https://doi.org/10.1093/femsyr/foaa035
Karim AS, Curran KA, Alper HS (2013) Characterization of plasmid burden and copy number in Saccharomyces cerevisiae for optimization of metabolic engineering applications. FEMS Yeast Res 13:107–116. https://doi.org/10.1111/1567-1364.12016
Knudsen J, Neergaard TBF, Gaigg B et al (2000) Role of Acyl-CoA binding protein in Acyl-CoA metabolism and acyl-CoA–mediated cell signaling. J Nutr 130:294S-298S. https://doi.org/10.1093/jn/130.2.294S
Larroude M, Celinska E, Back A et al (2018a) A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of β-carotene. Biotechnol Bioeng 115:464–472. https://doi.org/10.1002/bit.26473
Larroude M, Rossignol T, Nicaud J-M, Ledesma-Amaro R (2018b) Synthetic biology tools for engineering Yarrowia lipolytica. Biotechnol Adv 36:2150–2164. https://doi.org/10.1016/j.biotechadv.2018.10.004
Larroude M, Park Y, Soudier P et al (2019) A modular golden gate toolkit for Yarrowia lipolytica synthetic biology. Microb Biotechnol 12:1249–1259. https://doi.org/10.1111/1751-7915.13427
Larroude M, Trabelsi H, Nicaud J-M, Rossignol T (2020) A set of Yarrowia lipolytica CRISPR/Cas9 vectors for exploiting wild-type strain diversity. Biotechnol Lett 42:773–785. https://doi.org/10.1007/s10529-020-02805-4
Larroude M, Nicaud J-M, Rossignol T (2022) Golden gate multigene assembly method for Yarrowia lipolytica. Methods Mol Biol 2513:205–220. https://doi.org/10.1007/978-1-0716-2399-2_12
Leplat C, Nicaud J-M, Rossignol T (2015) High-throughput transformation method for Yarrowia lipolytica mutant library screening. FEMS Yeast Res 15:fov052. https://doi.org/10.1093/femsyr/fov052
Leplat C, Nicaud J-M, Rossignol T (2018) Overexpression screen reveals transcription factors involved in lipid accumulation in Yarrowia lipolytica. FEMS Yeast Res 18:foy037. https://doi.org/10.1093/femsyr/foy037
Lewis LK, Storici F, Van Komen S et al (2004) Role of the nuclease activity of Saccharomyces cerevisiae Mre11 in repair of DNA double-strand breaks in mitotic cells. Genetics 166:1701–1713. https://doi.org/10.1534/genetics.166.4.1701
Li H, Alper HS (2020) Producing biochemicals in Yarrowia lipolytica from xylose through a strain mating approach. Biotechnol J 15:e1900304. https://doi.org/10.1002/biot.201900304
Li Z, Qiao K, Liu N, Stephanopoulos G (2017) Engineering Yarrowia lipolytica for poly-3-hydroxybutyrate production. J Ind Microbiol Biotechnol 44:605–612. https://doi.org/10.1007/s10295-016-1864-1
Lin D, O’Callaghan CA (2020) Hierarchical modular DNA assembly using MetClo. Methods Mol Biol 2205:143–159. https://doi.org/10.1007/978-1-0716-0908-8_9
Liu L, Otoupal P, Pan A, Alper HS (2014) Increasing expression level and copy number of a Yarrowia lipolytica plasmid through regulated centromere function. FEMS Yeast Res 14(7):1124–1127. https://doi.org/10.1111/1567-1364.12201
Liu H, Madzak C, Sun M et al (2017) Engineering Yarrowia lipolytica for arachidonic acid production through rapid assembly of metabolic pathway. Biochem Eng J 119:52–58. https://doi.org/10.1016/j.bej.2016.12.004
Liu H, Wang C, Lu X et al (2019) Improved production of arachidonic acid by combined pathway engineering and synthetic enzyme fusion in Yarrowia lipolytica. J Agric Food Chem 67:9851–9857. https://doi.org/10.1021/acs.jafc.9b03727
Liu X, Cui Z, Su T et al (2022a) Identification of genome integration sites for developing a CRISPR-based gene expression toolkit in Yarrowia lipolytica. Microb Biotechnol 15:2223–2234. https://doi.org/10.1111/1751-7915.14060
Liu Z, Tian J, Miao Z et al (2022b) Metabolome and transcriptome profiling reveal carbon metabolic flux changes in Yarrowia lipolytica cells to rapamycin. J Fungi (basel) 8:939. https://doi.org/10.3390/jof8090939
Lopez C, Cao M, Yao Z, Shao Z (2021) Revisiting the unique structure of autonomously replicating sequences in Yarrowia lipolytica and its role in pathway engineering. Appl Microbiol Biotechnol 105:5959–5972. https://doi.org/10.1007/s00253-021-11399-4
Lv Y, Edwards H, Zhou J, Xu P (2019) Combining 26s rDNA and the Cre-IoxP system for iterative gene integration and efficient marker curation in Yarrowia lipolytica. ACS Synth Biol 8:568–576. https://doi.org/10.1021/acssynbio.8b00535
Ma J, Gu Y, Marsafari M, Xu P (2020) Synthetic biology, systems biology, and metabolic engineering of Yarrowia lipolytica toward a sustainable biorefinery platform. J Ind Microbiol Biotechnol 47:845–862. https://doi.org/10.1007/s10295-020-02290-8
Ma Y, Li J, Huang S, Stephanopoulos G (2021) Targeting pathway expression to subcellular organelles improves astaxanthin synthesis in Yarrowia lipolytica. Metab Eng 68:152–161. https://doi.org/10.1016/j.ymben.2021.10.004
Madzak C (2018) Engineering Yarrowia lipolytica for use in biotechnological applications: a review of major achievements and recent innovations. Mol Biotechnol 60:621–635. https://doi.org/10.1007/s12033-018-0093-4
Madzak C, Treton B, Blanchin-Roland S (2000) Strong hybrid promoters and integrative expression/secretion vectors for quasi-constitutive expression of heterologous proteins in the yeast Yarrowia lipolytica. J Mol Microbiol Biotechnol 2:207–216
Madzak C, Gaillardin C, Beckerich J-M (2004) Heterologous protein expression and secretion in the non-conventional yeast Yarrowia lipolytica: a review. J Biotechnol 109:63–81. https://doi.org/10.1016/j.jbiotec.2003.10.027
Mannaerts GP, Van Veldhoven PP (1993) Peroxisomal β-oxidation. Verh K Acad Geneeskd Belg 55:45–78
Markham KA, Palmer CM, Chwatko M et al (2018) Rewiring Yarrowia lipolytica toward triacetic acid lactone for materials generation. Proc Natl Acad Sci USA 115:2096–2101. https://doi.org/10.1073/pnas.1721203115
Marsafari M, Azi F, Dou S, Xu P (2022) Modular co-culture engineering of Yarrowia lipolytica for amorphadiene biosynthesis. Microb Cell Fact 21:279. https://doi.org/10.1186/s12934-022-02010-0
Misa J, Schwartz C (2021) CRISPR interference and activation to modulate transcription in Yarrowia lipolytica. Methods Mol Biol. https://doi.org/10.1007/978-1-0716-1414-3_6
Misa J, Schwartz C, Wheeldon I (2018) Design of hybrid RNA polymerase III promoters for efficient CRISPR-Cas9 function. Bio Protoc 8:e2779. https://doi.org/10.21769/BioProtoc.2779
Müller S, Sandal T, Kamp-Hansen P, Dalbøge H (1998) Comparison of expression systems in the yeasts Saccharomyces cerevisiae, Hansenula polymorpha, Klyveromyces lactis, Schizosaccharomyces pombe and Yarrowia lipolytica. Cloning of two novel promoters from Yarrowia lipolytica. Yeast 14:1267–1283. https://doi.org/10.1002/(SICI)1097-0061(1998100)14:14%3c1267::AID-YEA327%3e3.0.CO;2-2
Natter K, Leitner P, Faschinger A et al (2005) The spatial organization of lipid synthesis in the yeast Saccharomyces cerevisiae derived from large scale green fluorescent protein tagging and high resolution microscopy. Mol Cell Proteomics 4:662–672. https://doi.org/10.1074/mcp.M400123-MCP200
O’Halloran DM (2017) A guide to using STITCHER for overlapping assembly PCR applications. Methods Mol Biol. https://doi.org/10.1007/978-1-4939-6343-0_1
Ogrydziak DM, Scharf SJ (1982) Alkaline extracellular protease produced by Saccharomycopsis lipolytica CX161-1B. J Gen Microbiol 128:1225–1234. https://doi.org/10.1099/00221287-128-6-1225
Park H, Kim S (2021) Gene-specific mutagenesis enables rapid continuous evolution of enzymes in vivo. Nucleic Acids Res 49:e32–e32. https://doi.org/10.1093/nar/gkaa1231
Park Y-K, Dulermo T, Ledesma-Amaro R, Nicaud J-M (2018) Optimization of odd chain fatty acid production by Yarrowia lipolytica. Biotechnol Biofuels 11:158. https://doi.org/10.1186/s13068-018-1154-4
Park Y-K, Ledesma-Amaro R, Nicaud J-M (2019) De novo biosynthesis of odd-chain fatty acids in Yarrowia lipolytica enabled by modular pathway engineering. Front Bioeng Biotechnol 7:484. https://doi.org/10.3389/fbioe.2019.00484
Picataggio S (2009) Potential impact of synthetic biology on the development of microbial systems for the production of renewable fuels and chemicals. Curr Opin Biotechnol 20:325–329. https://doi.org/10.1016/j.copbio.2009.04.003
Qian Y, Tan S, Dong G et al (2020) Increased campesterol synthesis by improving lipid content in engineered Yarrowia lipolytica. Appl Microbiol Biotechnol 104:7165–7175. https://doi.org/10.1007/s00253-020-10743-4
Rigouin C, Gueroult M, Croux C et al (2017) Production of medium chain fatty acids by Yarrowia lipolytica: combining molecular design and TALEN to engineer the fatty acid synthase. ACS Synth Biol 6:1870–1879. https://doi.org/10.1021/acssynbio.7b00034
Rigouin C, Croux C, Borsenberger V et al (2018) Increasing medium chain fatty acids production in Yarrowia lipolytica by metabolic engineering. Microb Cell Fact 17:142. https://doi.org/10.1186/s12934-018-0989-5
Rigouin C, Croux C, Dubois G et al (2021) Genome editing in Y. lipolytica using TALENs. Methods Mol Biol. https://doi.org/10.1007/978-1-0716-1414-3_2
Rodriguez GM, Hussain MS, Gambill L et al (2016) Engineering xylose utilization in Yarrowia lipolytica by understanding its cryptic xylose pathway. Biotechnol Biofuels 9:149. https://doi.org/10.1186/s13068-016-0562-6
Røkke G, Korvald E, Pahr J et al (2014) BioBrick assembly standards and techniques and associated software tools. Methods Mol Biol 1116:1–24. https://doi.org/10.1007/978-1-62703-764-8_1
Rong L, Miao L, Wang S et al (2022) Engineering Yarrowia lipolytica to produce itaconic acid from waste cooking oil. Front Bioeng Biotechnol 10:888869. https://doi.org/10.3389/fbioe.2022.888869
Rutter CD, Zhang S, Rao CV (2015) Engineering Yarrowia lipolytica for production of medium-chain fatty acids. Appl Microbiol Biotechnol 99:7359–7368. https://doi.org/10.1007/s00253-015-6764-1
Schwartz C, Shabbir-Hussain M, Frogue K et al (2017) Standardized markerless gene integration for pathway engineering in Yarrowia lipolytica. ACS Synth Biol 6:402–409. https://doi.org/10.1021/acssynbio.6b00285
Schwartz C, Curtis N, Löbs A-K, Wheeldon I (2018) Multiplexed CRISPR activation of cryptic sugar metabolism enables Yarrowia lipolytica growth on cellobiose. Biotechnol J 13:e1700584. https://doi.org/10.1002/biot.201700584
Shabbir Hussain M, Rodriguez MG, Gao D et al (2016) Recent advances in bioengineering of the oleaginous yeast Yarrowia lipolytica. AIMS Bioeng 3:493–514. https://doi.org/10.3934/bioeng.2016.4.493
Shabbir Hussain M, Wheeldon I, Blenner MA (2017) A strong hybrid fatty acid inducible transcriptional sensor built from Yarrowia lipolytica upstream activating and regulatory sequences. Biotechnol J. https://doi.org/10.1002/biot.201700248
Shaw D, Miravet-Verde S, Piñero-Lambea C et al (2021) LoxTnSeq: random transposon insertions combined with cre/lox recombination and counterselection to generate large random genome reductions. Microb Biotechnol 14:2403–2419. https://doi.org/10.1111/1751-7915.13714
Siewers V (2014) An overview on selection marker genes for transformation of Saccharomyces cerevisiae. Methods Mol Biol 1152:3–15. https://doi.org/10.1007/978-1-4939-0563-8_1
Sun W, Yang Z, Xu P (2021) Engineering Yarrowia lipolytica for production of fatty alcohols with yalibrick vectors. Methods Mol Biol 2307:159–173. https://doi.org/10.1007/978-1-0716-1414-3_11
Sun M, Shi T, Lin L et al (2022) Advancing Yarrowia lipolytica as a superior biomanufacturing platform by tuning gene expression using promoter engineering. Bioresour Technol 347:126717. https://doi.org/10.1016/j.biortech.2022.126717
Tai M, Stephanopoulos G (2013) Engineering the push and pull of lipid biosynthesis in oleaginous yeast Yarrowia lipolytica for biofuel production. Metab Eng 15:1–9. https://doi.org/10.1016/j.ymben.2012.08.007
Tan X, Letendre JH, Collins JJ, Wong WW (2021) Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics. Cell 184:881–898. https://doi.org/10.1016/j.cell.2021.01.017
Titorenko VI, Rachubinski RA (1998) Mutants of the yeast Yarrowia lipolytica defective in protein exit from the endoplasmic reticulum are also defective in peroxisome biogenesis. Mol Cell Biol 18:2789–2803. https://doi.org/10.1128/MCB.18.5.2789
Tran KM, Lee H-M, Thai TD et al (2021) Synthetically engineered microbial scavengers for enhanced bioremediation. J Hazard Mater 419:126516. https://doi.org/10.1016/j.jhazmat.2021.126516
Trassaert M, Vandermies M, Carly F et al (2017) New inducible promoter for gene expression and synthetic biology in Yarrowia lipolytica. Microb Cell Fact 16:141. https://doi.org/10.1186/s12934-017-0755-0
Tsakraklides V (2021) Targeted integration through transformation of hydroxyurea-arrested cells. Methods Mol Biol. https://doi.org/10.1007/978-1-0716-1414-3_9
Tsakraklides V, Brevnova E, Stephanopoulos G, Shaw AJ (2015) Improved gene targeting through cell cycle synchronization. PLoS ONE 11:e0133434. https://doi.org/10.1371/journal.pone.0133434
Vandermies M, Denies O, Nicaud J-M, Fickers P (2017) EYK1 encoding erythrulose kinase as a catabolic selectable marker for genome editing in the non-conventional yeast Yarrowia lipolytica. J Microbiol Methods 139:161–164. https://doi.org/10.1016/j.mimet.2017.05.012
Vernis L, Abbas A, Chasles M et al (1997) An origin of replication and a centromere are both needed to establish a replicative plasmid in the yeast Yarrowia lipolytica. Mol Cell Biol 17:1995–2004. https://doi.org/10.1128/MCB.17.4.1995
Wagner JM, Williams EV, Alper HS (2018) Developing a piggyBac transposon system and compatible selection markers for insertional mutagenesis and genome engineering in Yarrowia lipolytica. Biotechnol J 13:e1800022. https://doi.org/10.1002/biot.201800022
Walther TC, Farese RV (2012) Lipid droplets and cellular lipid metabolism. Annu Rev Biochem 81:687–714. https://doi.org/10.1146/annurev-biochem-061009-102430
Wang W, Blenner MA (2022) Engineering heterologous enzyme secretion in Yarrowia lipolytica. Microb Cell Fact 21:134. https://doi.org/10.1186/s12934-022-01863-9
Wang Z, Zheng W, Ma W (2003) Gateway cloning system: recent advance of DNA recombination technology. China Biotechnol. https://doi.org/10.13523/j.cb.20030706
Wang L, Deng A, Zhang Y et al (2018) Efficient CRISPR-Cas9 mediated multiplex genome editing in yeasts. Biotechnol Biofuels 11:277. https://doi.org/10.1186/s13068-018-1271-0
Wang K, Shi T, Lin L et al (2022) Advances in synthetic biology tools paving the way for the biomanufacturing of unusual fatty acids using the Yarrowia lipolytica chassis. Biotechnol Adv 59:107984. https://doi.org/10.1016/j.biotechadv.2022.107984
Wang C, Lin M, Yang Z et al (2023) Characterization of the endogenous promoters in Yarrowia lipolytica for the biomanufacturing applications. Process Biochem 124:245–252. https://doi.org/10.1016/j.procbio.2022.11.023
Wei H, Wang W, Alper HS et al (2019) Ameliorating the metabolic burden of the co-expression of secreted fungal cellulases in a high lipid-accumulating Yarrowia lipolytica strain by medium C/N ratio and a chemical chaperone. Front Microbiol 9:3276. https://doi.org/10.3389/fmicb.2018.03276
Wei W, Shang Y, Zhang P et al (2020) Engineering prokaryotic transcriptional activator XylR as a xylose-inducible biosensor for transcription activation in yeast. ACS Synth Biol 9:1022–1029. https://doi.org/10.1021/acssynbio.0c00122
Wong L, Engel J, Jin E et al (2017) YaliBricks, a versatile genetic toolkit for streamlined and rapid pathway engineering in Yarrowia lipolytica. Metab Eng Commun 5:68–77. https://doi.org/10.1016/j.meteno.2017.09.001
Xiong X, Chen S (2020) Expanding toolbox for genes expression of Yarrowia lipolytica to include novel inducible, repressible, and hybrid promoters. ACS Synth Biol 9:2208–2213. https://doi.org/10.1021/acssynbio.0c00243
Xu P, Qiao K, Ahn WS, Stephanopoulos G (2016) Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals. Proc Natl Acad Sci USA 113:10848–10853. https://doi.org/10.1073/pnas.1607295113
Yan FX, Dong GR, Qiang S et al (2020) Overexpression of Δ12, Δ15-desaturases for enhanced lipids synthesis in Yarrowia lipolytica. Front Microbiol 11:289. https://doi.org/10.3389/fmicb.2020.00289
Yang Z, Xu P (2021) Implementing CRISPR-Cas12a for efficient genome editing in Yarrowia lipolytica. Methods Mol Biol. https://doi.org/10.1007/978-1-0716-1414-3_7
Yang K, Qiao Y, Li F et al (2019) Subcellular engineering of lipase dependent pathways directed towards lipid related organelles for highly effectively compartmentalized biosynthesis of triacylglycerol derived products in Yarrowia lipolytica. Metab Eng 55:231–238. https://doi.org/10.1016/j.ymben.2019.08.001
Yang Z, Edwards H, Xu P (2020) CRISPR-Cas12a/Cpf1-assisted precise, efficient and multiplexed genome-editing in Yarrowia lipolytica. Metab Eng Commun 10:e00112. https://doi.org/10.1016/j.mec.2019.e00112
Yuzbasheva EY, Agrimi G, Yuzbashev TV et al (2019) The mitochondrial citrate carrier in Yarrowia lipolytica: Its identification, characterization and functional significance for the production of citric acid. Metab Eng 54:264–274. https://doi.org/10.1016/j.ymben.2019.05.002
Yuzbasheva EY, Scarcia P, Yuzbashev TV et al (2021) Engineering Yarrowia lipolytica for the selective and high-level production of isocitric acid through manipulation of mitochondrial dicarboxylate–tricarboxylate carriers. Metab Eng 65:156–166. https://doi.org/10.1016/j.ymben.2020.11.001
Zahid S, Seif El Dahan M, Iehl F et al (2021) The multifaceted roles of Ku70/80. Int J Mol Sci 22:4134. https://doi.org/10.3390/ijms22084134
Zeng S, Liu H, Shi T et al (2018) Recent advances in metabolic engineering of Yarrowia lipolytica for lipid overproduction. Eur J Lipid Sci Technol 120:1700352. https://doi.org/10.1002/ejlt.201700352
Zetsche B, Gootenberg JS, Abudayyeh OO et al (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163:759–771. https://doi.org/10.1016/j.cell.2015.09.038
Zhang B, Chen H, Li M et al (2013) Genetic engineering of Yarrowia lipolytica for enhanced production of trans-10, cis-12 conjugated linoleic acid. Microb Cell Fact 12:70. https://doi.org/10.1186/1475-2859-12-70
Zhang J, Cao Y, Peng Y et al (2019) High production of fatty alcohols in Yarrowia lipolytica by coordination with glycolysis. Sci China Chem 62:1007–1016. https://doi.org/10.1007/s11426-019-9456-y
Zhang C, Li M, Zhao G, Lu W (2020) Harnessing yeast peroxisomes and cytosol acetyl-CoA for sesquiterpene α-humulene production. J Agric Food Chem 68:1382–1389. https://doi.org/10.1021/acs.jafc.9b07290
Zhang P, Wei W, Zhou Y, Ye B (2021) Construction of a light-controlled expression system and its application in Yarrowia lipolytica. SynbioJ. https://doi.org/10.12211/2096-8280.2021-018
Zhang J, Cui Z, Qi Q, Hou J (2022) The recent advances in developing gene editing and expression tools and the synthesis of natural products in Yarrowia lipolytica. CJB 38:478–505. https://doi.org/10.13345/j.cjb.210327
Zhao C, Cui Z, Zhao X et al (2019) Enhanced itaconic acid production in Yarrowia lipolytica via heterologous expression of a mitochondrial transporter MTT. Appl Microbiol Biotechnol 103:2181–2192. https://doi.org/10.1007/s00253-019-09627-z
Zhao Y, Liu S, Lu Z et al (2021) Hybrid promoter engineering strategies in Yarrowia lipolytica: isoamyl alcohol production as a test study. Biotechnol Biofuels 14:149. https://doi.org/10.1186/s13068-021-02002-z
Zhou Q, Jiao L, Li W et al (2021) A novel Cre/lox-based genetic tool for repeated, targeted and markerless gene integration in Yarrowia lipolytica. Int J Mol Sci 22:10739. https://doi.org/10.3390/ijms221910739
Funding
This work was supported by the Fundamental Research Funds for the Central Universities (Project No.2572022BD03), the National Natural Science Foundation of China (Project No. 31900064), the Undergraduate Training Programs for Innovations by NEFU (Project No. 202210225121).
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception, material preparation, data collection and analysis. The first draft of the manuscript was written by all authors. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors have no relevant financial or non-financial interests to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Cao, L., Li, J., Yang, Z. et al. A review of synthetic biology tools in Yarrowia lipolytica. World J Microbiol Biotechnol 39, 129 (2023). https://doi.org/10.1007/s11274-023-03557-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11274-023-03557-9