Genome and metabolic engineering in non-conventional yeasts: Current advances and applications

Synthetic and Systems Biotechnology

Volumn 2, Issue 3, 2017, Pages 198-207

  Löbs, Ann Kathrin ^a   Schwartz, Cory ^a   Wheeldon, Ian ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

CRISPR Cas9; Hansenula polymorpha; Kluyveromyces lactis; Kluyveromyces marxianus; Pichia pastoris; Scheffersomyces stipitis; Yarrowia lipolytica

Indexed keywords

2 OXOGLUTARIC ACID; ACETIC ACID ETHYL ESTER; ALCOHOL; ALPHA INTERFERON; AMYLASE; BETA GALACTOSIDASE; BETA MANNOSIDASE; CHYMOSIN; CITRIC ACID; ECALLANTIDE; FUMARIC ACID; GLUCOSE; GLYCOLIC ACID; HEPATITIS B SURFACE ANTIGEN; HUMAN SERUM ALBUMIN; ICOSAPENTAENOIC ACID; INSULIN; INTERLEUKIN 1BETA; INULINASE; LACTIC ACID; LIPID; LYCOPENE; OCRIPLASMIN; PHYTASE; POLYGALACTURONASE; PROTEINASE; TRIACYLGLYCEROL LIPASE; TRYPSIN; UNINDEXED DRUG; XYLITOL;

CARBON FIXATION; CRISPR-CAS9 SYSTEM; GENE EDITING; GENETIC ENGINEERING; HEAT TOLERANCE; HOMOLOGOUS RECOMBINATION; KLUYVEROMYCES LACTIS; KLUYVEROMYCES MARXIANUS; KOMAGATAELLA PASTORIS; METABOLIC ENGINEERING; NONHUMAN; OGATAEA ANGUSTA; PROTEIN SECRETION; REVIEW; SACCHAROMYCES CEREVISIAE; SCHEFFERSOMYCES STIPITIS; TRANSCRIPTION REGULATION; YARROWIA LIPOLYTICA; YEAST;

EID: 85047013671     PISSN: None     EISSN: 2405805X     Source Type: Journal    
DOI: 10.1016/j.synbio.2017.08.002     Document Type: Review

References (119)

1. Qiu, Z., Jiang, R., Improving Saccharomyces cerevisiae ethanol production and tolerance via RNA polymerase II subunit Rpb7. Biotechnol Biofuels, 10, 2017, 125.
2. Nielsen, J., Larsson, C., van Maris, A., Pronk, J., Metabolic engineering of yeast for production of fuels and chemicals. Curr Opin Biotechnol 24:3 (2013), 398–404.
3. Wagner, J.M., Alper, H.S., Synthetic biology and molecular genetics in non-conventional yeasts: current tools and future advances. Fungal Genet Biol 89 (2016), 126–136.
4. Spohner, S.C., Schaum, V., Quitmann, H., Czermak, P., Kluyveromyces lactis: an emerging tool in biotechnology. J Biotechnol 222 (2016), 104–116.
5. Varela, J.A., Gethins, L., Stanton, C., Ross, P., Morrissey, J.P., Applications of Kluyveromyces marxianus in biotechnology. Satyanarayana, T., Kunze, G., (eds.) Yeast diversity in human welfare, 2017, Springer, Singapore, 439–453.
6. Lobs, A.K., Lin, J.L., Cook, M., Wheeldon, I., High throughput, colorimetric screening of microbial ester biosynthesis reveals high ethyl acetate production from Kluyveromyces marxianus on C5, C6, and C12 carbon sources. Biotechnol J 11:10 (2016), 1274–1281.
7. Loser, C., Urit, T., Stukert, A., Bley, T., Formation of ethyl acetate from whey by Kluyveromyces marxianus on a pilot scale. J Biotechnol 163:1 (2013), 17–23.
8. Loser, C., Urit, T., Keil, P., Bley, T., Studies on the mechanism of synthesis of ethyl acetate in Kluyveromyces marxianus DSM 5422. Appl Microbiol Biotechnol 99:3 (2014), 1131–1144.
9. Agbogbo, F.K., Coward-Kelly, G., Cellulosic ethanol production using the naturally occurring xylose-fermenting yeast, Pichia stipitis. Biotechnol Lett 30:9 (2008), 1515–1524.
10. Dupreez, J.C., Bosch, M., Prior, B.A., The fermentation of hexose and pentose sugars by Candida-Shehatae and Pichia-stipitis. Appl Microbiol Biotechnol 23:3–4 (1986), 228–233.
11. Blazeck, J., Hill, A., Liu, L.Q., Knight, R., Miller, J., Pan, A., et al. Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production. Nat Commun, 2014, 5.
12. Hussain, M.S., Rodriguez, G.M., Gao, D.F., Spagnuolo, M., Gambill, L., Blenner, M., Recent advances in bioengineering of the oleaginous yeast Yarrowia lipolytica. Aims Bioeng 3:4 (2016), 493–514.
13. Beopoulos, A., Cescut, J., Haddouche, R., Uribelarrea, J.L., Molina-Jouve, C., Nicaud, J.M., Yarrowia lipolytica as a model for bio-oil production. Prog Lipid Res 48:6 (2009), 375–387.
14. van der Klei, I.J., Yurimoto, H., Sakai, Y., Veenhuis, M., The significance of peroxisomes in methanol metabolism in methylotrophic yeast. Bba-Mol Cell Res 1763:12 (2006), 1453–1462.
15. Siverio, J.M., Assimilation of nitrate by yeasts. Fems Microbiol Rev 26:3 (2002), 277–284.
16. Gellissen, G., Heterologous protein production in methylotrophic yeasts. Appl Microbiol Biotechnol 54:6 (2000), 741–750.
17. Dmytruk, K., Kurylenko, O., Ruchala, J., Ishchuk, O., Sibirny, A., Development of the thermotolerant methylotrophic yeast Hansenula polymorpha as efficient ethanol producer. Yeast diversity in human welfare, 2017, Springer, 257–282.
18. Gellissen, G., Kunze, G., Gaillardin, C., Cregg, J.M., Berardi, E., Veenhuis, M., et al. New yeast expression platforms based on methylotrophic Hansenula polymorpha and Pichia pastoris and on dimorphic Arxula adeninivorans and Yarrowia lipolytica - a comparison. Fems Yeast Res 5:11 (2005), 1079–1096.
19. Jahic, M., Veide, A., Charoenrat, T., Teeri, T., Enfors, S.O., Process technology for production and recovery of heterologous proteins with Pichia pastoris. Biotechnol Prog 22:6 (2006), 1465–1473.
20. Byme, B., Pichia pastoris as an expression host for membrane protein structural biology. Curr Opin Struct Biol 32 (2015), 9–17.
21. Dmytruk, K.V., Kurylenko, O.O., Ruchala, J., Abbas, C.A., Sibirny, A.A., Genetic improvement of conventional and nonconventional yeasts for the production of first-and second-generation ethanol. Biotechnology of yeasts and filamentous fungi, 2017, Springer, 1–38.
22. Walsh, G., Biopharmaceutical benchmarks 2014. Nat Biotechnol 32:10 (2014), 992–1000.
23. Ahmad, M., Hirz, M., Pichler, H., Schwab, H., Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production. Appl Microbiol Biotechnol 98:12 (2014), 5301–5317.
24. Lane, M.M., Morrissey, J.P., Kluyveromyces marxianus: a yeast emerging from its sister's shadow. Fungal Biol Rev 24:1 (2010), 17–26.
25. Mead, D.J., Gardner, D.C.J., Oliver, S.G., The yeast 2-Mu plasmid - strategies for the survival of a selfish DNA. Mol Mol Gen Genet 205:3 (1986), 417–421.
26. Lee, M.E., DeLoache, W.C., Cervantes, B., Dueber, J.E., A highly characterized yeast toolkit for modular, multipart assembly. ACS Synth Biol 4:9 (2015), 975–986.
27. Cao, M., Gao, M., Lopez-Garcia, C.L., Wu, Y., Seetharam, A.S., Severin, A.J., et al. Centromeric DNA facilitates nonconventional yeast genetic engineering. ACS Synth Biol 6:8 (2017), 1545–1553.
28. Jensen, N.B., Strucko, T., Kildegaard, K.R., David, F., Maury, J., Mortensen, U.H., et al. EasyClone: method for iterative chromosomal integration of multiple genes in Saccharomyces cerevisiae. Fems Yeast Res 14:2 (2014), 238–248.
29. Vernis, L., Poljak, L., Chasles, M., Uchida, K., Casaregola, S., Kas, E., et al. Only centromeres can supply the partition system required for ARS function in the yeast Yarrowia lipolytica. J Mol Biol 305:2 (2001), 203–217.
30. Da Silva, N.A., Srikrishnan, S., Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. Fems Yeast Res 12:2 (2012), 197–214.
31. Kegel, A., Martinez, P., Carter, S.D., Astrom, S.U., Genome wide distribution of illegitimate recombination events in Kluyveromyces lactis. Nucleic Acids Res 34:5 (2006), 1633–1645.
32. Lieber, M.R., The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79 (2010), 181–211.
33. Flagfeldt, D.B., Siewers, V., Huang, L., Nielsen, J., Characterization of chromosomal integration sites for heterologous gene expression in Saccharomyces cerevisiae. Yeast 26:10 (2009), 545–551.
34. Shao, Z., Zhao, H., Zhao, H., DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res, 37(2), 2009, e16.
35. Horwitz, A.A., Walter, J.M., Schubert, M.G., Kung, S.H., Hawkins, K., Platt, D.M., et al. Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR-Cas. Cell Syst 1:1 (2015), 88–96.
36. Schwartz, C., Shabbir-Hussain, M., Frogue, K., Blenner, M., Wheeldon, I., Standardized markerless gene integration for pathway engineering in Yarrowia lipolytica. ACS Synth Biol 6:3 (2017), 402–409.
37. Sauer, B., Functional expression of the cre-lox site-specific recombination system in the yeast Saccharomyces cerevisiae. Mol Cell Biol 7:6 (1987), 2087–2096.
38. Alani, E., Cao, L., Kleckner, N., A method for gene disruption that allows repeated use of Ura3 selection in the construction of multiply disrupted yeast strains. Genetics 116:4 (1987), 541–545.
39. Cheon, S.A., Choo, J., Ubiyvovk, V.M., Park, J.N., Kim, M.W., Oh, D.B., et al. New selectable host-marker systems for multiple genetic manipulations based on TRP1, MET2 and ADE2 in the methylotrophic yeast Hansenula polymorpha. Yeast 26:9 (2009), 507–521.
40. Pecota, D.C., Rajgarhia, V., Da Silva, N.A., Sequential gene integration for the engineering of Kluyveromyces marxianus. J Biotechnol 127:3 (2007), 408–416.
41. Pan, R.Q., Zhang, J., Shen, W.L., Tao, Z.Q., Li, S.P., Yan, X., Sequential deletion of Pichia pastoris genes by a self-excisable cassette. Fems Yeast Res 11:3 (2011), 292–298.
42. Laplaza, J.M., Torres, B.R., Jin, Y.S., Jeffries, T.W., Sh ble and Cre adapted for functional genomics and metabolic engineering of Pichia stipitis. Enzyme Microb Tech 38:6 (2006), 741–747.
43. Steensma, H.Y., Ter Linde, J.J.M., Plasmids with the Cre-recombinase and the dominant nat marker, suitable for use in prototrophic strains of Saccharomyces cerevisiae and Kluyveromyces lactis. Yeast 18:5 (2001), 469–472.
44. Kooistra, R., Hooykaas, P.J., Steensma, H.Y., Efficient gene targeting in Kluyveromyces lactis. Yeast 21:9 (2004), 781–792.
45. Maassen, N., Freese, S., Schruff, B., Passoth, V., Klinner, U., Nonhomologous end joining and homologous recombination DNA repair pathways in integration mutagenesis in the xylose-fermenting yeast Pichia stipitis. Fems Yeast Res 8:5 (2008), 735–743.
46. Verbeke, J., Beopoulos, A., Nicaud, J.M., Efficient homologous recombination with short length flanking fragments in Ku70 deficient Yarrowia lipolytica strains. Biotechnol Lett 35:4 (2013), 571–576.
47. Kretzschmar, A., Otto, C., Holz, M., Werner, S., Hubner, L., Barth, G., Increased homologous integration frequency in Yarrowia lipolytica strains defective in non-homologous end-joining. Curr Genet 59:1–2 (2013), 63–72.
48. Saraya, R., Krikken, A.M., Kiel, J.A., Baerends, R.J., Veenhuis, M., van der Klei, I.J., Novel genetic tools for Hansenula polymorpha. Fems Yeast Res 12:3 (2012), 271–278.
49. Naatsaari, L., Mistlberger, B., Ruth, C., Hajek, T., Hartner, F.S., Glieder, A., Deletion of the Pichia pastoris KU70 homologue facilitates platform strain generation for gene expression and synthetic biology. PLoS One, 7(6), 2012, e39720.
50. Abdel-Banat, B.M., Nonklang, S., Hoshida, H., Akada, R., Random and targeted gene integrations through the control of non-homologous end joining in the yeast Kluyveromyces marxianus. Yeast 27:1 (2010), 29–39.
51. Choo, J.H., Han, C., Kim, J.Y., Kang, H.A., Deletion of a KU80 homolog enhances homologous recombination in the thermotolerant yeast Kluyveromyces marxianus. Biotechnol Lett 36:10 (2014), 2059–2067.
52. Chapman, J.R., Taylor, M.R.G., Boulton, S.J., Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47:4 (2012), 497–510.
53. Tsakraklides, V., Brevnova, E., Stephanopoulos, G., Shaw, A.J., Improved gene targeting through cell cycle synchronization. PLoS One, 10(7), 2015, e0133434.
54. Liu, Z., Liang, Y., Ang, E.L., Zhao, H., A new era of genome integration-simply cut and paste!. ACS Synth Biol 6:4 (2017), 601–609.
55. David, F., Siewers, V., Advances in yeast genome engineering. Fems Yeast Res 15:1 (2015), 1–14.
56. Rigouin, C., Gueroult, M., Croux, C., Dubois, G., Borsenberger, V., Barbe, S., et al. Production of medium chain fatty acids by Yarrowia lipolytica: combining molecular design and TALEN to engineer the fatty acid synthase. ACS Synth Biol, 2017, 10.1021/acssynbio.7b00034 Article ASAP.
57. DiCarlo, J.E., Norville, J.E., Mali, P., Rios, X., Aach, J., Church, G.M., Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems. Nucleic Acids Res 41:7 (2013), 4336–4343.
58. Stovicek, V., Holkenbrink, C., Borodina, I., CRISPR/Cas system for yeast genome engineering: advances and applications. Fems Yeast Res, 17(5), 2017 fox030.
59. Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., Charpentier, E., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:6096 (2012), 816–821.
60. Gao, S., Tong, Y., Wen, Z., Zhu, L., Ge, M., Chen, D., et al. Multiplex gene editing of the Yarrowia lipolytica genome using the CRISPR-Cas9 system. J Ind Microbiol 43:8 (2016), 1085–1093.
61. Schwartz, C.M., Hussain, M.S., Blenner, M., Wheeldon, I., Synthetic RNA polymerase III promoters facilitate high-efficiency CRISPR-Cas9-mediated genome editing in Yarrowia lipolytica. ACS Synth Biol 5:4 (2016), 356–359.
62. Lobs, A.K., Engel, R., Schwartz, C., Flores, A., Wheeldon, I., CRISPR-Cas9-enabled genetic disruptions for understanding ethanol and ethyl acetate biosynthesis in Kluyveromyces marxianus. Biotechnol Biofuels, 10, 2017, 164.
63. Weninger, A., Hatzl, A.M., Schmid, C., Vogl, T., Glieder, A., Combinatorial optimization of CRISPR/Cas9 expression enables precision genome engineering in the methylotrophic yeast Pichia pastoris. J Biotechnol 235 (2016), 139–149.
64. Numamoto, M., Maekawa, H., Kaneko, Y., Efficient genome editing by CRISPR/Cas9 with a tRNA-sgRNA fusion in the methylotrophic yeast Ogataea polymorpha. J Biosci Bioeng, 2017, 10.1016/j.jbiosc.2017.06.001 (in press).
65. Qi, L.S., Larson, M.H., Gilbert, L.A., Doudna, J.A., Weissman, J.S., Arkin, A.P., et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152:5 (2013), 1173–1183.
66. Smith, J.D., Suresh, S., Schlecht, U., Wu, M., Wagih, O., Peltz, G., et al. St Onge RP: quantitative CRISPR interference screens in yeast identify chemical-genetic interactions and new rules for guide RNA design. Genome Biol, 17, 2016, 45.
67. Gilbert, L.A., Larson, M.H., Morsut, L., Liu, Z., Brar, G.A., Torres, S.E., et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:2 (2013), 442–451.
68. Schwartz, C., Frogue, K., Ramesh, A., Misa, J., Wheeldon, I., CRISPRi repression of nonhomologous end-joining for enhanced genome engineering via homologous recombination in Yarrowia lipolytica. Biotechnol Bioeng, 2017, 10.1002/bit.26404 Accepted Author Manuscript.
69. Gilbert, L.A., Larson, M.H., Morsut, L., Liu, Z.R., Brar, G.A., Torres, S.E., et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:2 (2013), 442–451.
70. Etschmann, M.M.W., Schrader, J., An aqueous-organic two-phase bioprocess for efficient production of the natural aroma chemicals 2-phenylethanol and 2-phenylethylacetate with yeast. Appl Microbiol Biotechnol 71:4 (2006), 440–443.
71. Madzak, C., Yarrowia lipolytica: recent achievements in heterologous protein expression and pathway engineering. Appl Microbiol Biotechnol 99:11 (2015), 4559–4577.
72. Xue, Z., Sharpe, P.L., Hong, S.P., Yadav, N.S., Xie, D., Short, D.R., et al. Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica. Nat Biotechnol 31:8 (2013), 734–740.
73. Wei, L., Liu, J., Qi, H.S., Wen, J.P., Engineering Scheffersomyces stipitis for fumaric acid production from xylose. Bioresour Technol 187 (2015), 246–254.
74. Ilmen, M., Koivuranta, K., Ruohonen, L., Suominen, P., Penttila, M., Efficient production of L-lactic acid from xylose by Pichia stipitis. Appl Environ Microbiol 73:1 (2007), 117–123.
75. Dashtban, M., Wen, X., Bajwa, P.K., Ho, C.Y., Lee, H., Deletion of hxk1 gene results in derepression of xylose utilization in Scheffersomyces stipitis. J Ind Microbiol 42:6 (2015), 889–896.
76. Kunze, G., Kang, H.A., Gellissen, G., Hansenula polymorpha (Pichia angusta): biology and applications. Yeast biotechnology: diversity and applications, 2009, Springer, 47–64.
77. Spohner, S.C., Muller, H., Quitmann, H., Czermak, P., Expression of enzymes for the usage in food and feed industry with Pichia pastoris. J Biotechnol 202 (2015), 118–134.
78. Wriessnegger, T., Augustin, P., Engleder, M., Leitner, E., Muller, M., Kaluzna, I., et al. Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris. Metab Eng 24 (2014), 18–29.
79. Geier, M., Fauland, P., Vogl, T., Glieder, A., Compact multi-enzyme pathways in P. pastoris. Chem Commun 51:9 (2015), 1643–1646.
80. Vandenberg, J.A., Vanderlaken, K.J., Vanooyen, A.J.J., Renniers, T.C.H.M., Rietveld, K., Schaap, A., et al. Kluyveromyces as a host for heterologous gene-expression - expression and secretion of prochymosin. Bio-Technol 8:2 (1990), 135–139.
81. Colussi, P.A., Taron, C.H., Kluyveromyces lactis LAC4 promoter variants that lack function in bacteria but retain full function in K. lactis. Appl Environ Microbiol 71:11 (2005), 7092–7098.
82. Almeida, C.M., Gomes, D., Faro, C., Simoes, I., Engineering a cardosin B-derived rennet for sheep and goat cheese manufacture. Appl Microbiol Biotechnol 99:1 (2015), 269–281.
83. Jo, H.J., Noh, J.S., Kong, K.H., Efficient secretory expression of the sweet-tasting protein brazzein in the yeast Kluyveromyces lactis. Protein Expres Purif 90:2 (2013), 84–89.
84. Kim, T.Y., Lee, S.W., Oh, M.K., Biosynthesis of 2-phenylethanol from glucose with genetically engineered Kluyveromyces marxianus. Enzyme Microb Technol 61–62 (2014), 44–47.
85. Ballesteros, M., Oliva, J.M., Negro, M.J., Manzanares, P., Ballesteros, I., Ethanol from lignocellulosic materials by a simultaneous saccharification and fermentation process (SFS) with Kluyveromyces marxianus CECT 10875. Process Biochem 39:12 (2004), 1843–1848.
86. Zafar, S., Owais, M., Ethanol production from crude whey by Kluyveromyces marxianus. Biochem Eng J 27:3 (2006), 295–298.
87. Zhang, J., Zhang, B., Wang, D.M., Gao, X.L., Sun, L.H., Hong, J., Rapid ethanol production at elevated temperatures by engineered thermotolerant Kluyveromyces marxianus via the NADP(H)-preferring xylose reductase-xylitol dehydrogenase pathway. Metab Eng 31 (2015), 140–152.
88. Yanase, S., Hasunuma, T., Yamada, R., Tanaka, T., Ogino, C., Fukuda, H., et al. Direct ethanol production from cellulosic materials at high temperature using the thermotolerant yeast Kluyveromyces marxianus displaying cellulolytic enzymes. Appl Microbiol Biotechnol 88:1 (2010), 381–388.
89. Wang, R.L., Li, L.L., Zhang, B., Gao, X.L., Wang, D.M., Hong, J., Improved xylose fermentation of Kluyveromyces marxianus at elevated temperature through construction of a xylose isomerase pathway. J Ind Microbiol 40:8 (2013), 841–854.
90. Cheon, Y., Kim, J.S., Park, J.B., Heo, P., Lim, J.H., Jung, G.Y., et al. A biosynthetic pathway for hexanoic acid production in Kluyveromyces marxianus. J Biotechnol 182 (2014), 30–36.
91. Slininger, P.J., Shea-Andersh, M.A., Thompson, S.R., Dien, B.S., Kurtzman, C.P., Balan, V., et al. Evolved strains of Scheffersomyces stipitis achieving high ethanol productivity on acid- and base-pretreated biomass hydrolyzate at high solids loading. Biotechnol Biofuels, 8, 2015, 60.
92. Shi, J., Zhang, M., Zhang, L., Wang, P., Jiang, L., Deng, H., Xylose-fermenting Pichia stipitis by genome shuffling for improved ethanol production. Microb Biotechnol 7:2 (2014), 90–99.
93. Pereira, S.R., Sanchez, I.N.V., Frazao, C.J., Serafim, L.S., Gorwa-Grauslund, M.F., Xavier, A.M., Adaptation of Scheffersomyces stipitis to hardwood spent sulfite liquor by evolutionary engineering. Biotechnol Biofuels, 8, 2015, 50.
94. Zhang, W., Geng, A.L., Improved ethanol production by a xylose-fermenting recombinant yeast strain constructed through a modified genome shuffling method. Biotechnol Biofuels, 2012, 5.
95. Hughes, S.R., Gibbons, W.R., Bang, S.S., Pinkelman, R., Bischoff, K.M., Slininger, P.J., et al. Random UV-C mutagenesis of Scheffersomyces (formerly Pichia) stipitis NRRL Y-7124 to improve anaerobic growth on lignocellulosic sugars. J Ind Microbiol 39:1 (2012), 163–173.
96. Rodriguez, G.M., Hussain, M.S., Gambill, L., Gao, D.F., Yaguchi, A., Blenner, M., Engineering xylose utilization in Yarrowia lipolytica by understanding its cryptic xylose pathway. Biotechnol Biofuels, 9, 2016.
97. Xu, J., Liu, N., Qiao, K., Vogg, S., Stephanopoulos, G., Application of metabolic controls for the maximization of lipid production in semicontinuous fermentation. Proc Natl Acad Sci U. S. A 114:27 (2017), E5308–E5316.
98. Qiao, K.J., Wasylenko, T.M., Zhou, K., Xu, P., Stephanopoulos, G., Lipid production in Yarrowia lipolytica is maximized by engineering cytosolic redox metabolism. Nat Biotechnol 35:2 (2017), 173–177.
99. Gellissen, G., Veenhuis, M., The methylotrophic yeast Hansenula polymorpha: its use in fundamental research and as a cell factory. Yeast, 18(3), 2001 i-iii.
100. Ballou, C.E., Isolation, characterization, and properties of Saccharomyces cerevisiae mnn mutants with nonconditional protein glycosylation defects. Methods Enzymol 185 (1990), 440–470.
101. Cheon, S.A., Kim, H., Oh, D.B., Kwon, O., Kang, H.A., Remodeling of the glycosylation pathway in the methylotrophic yeast Hansenula polymorpha to produce human hybrid-type N-glycans. J Microbiol 50:2 (2012), 341–348.
102. Muller, F. II, Tieke, A., Waschk, D., Muhle, C., Muller, I.F., Seigelchifer, M., et al. Production of IFN alpha-2a in Hansenula polymorpha. Process Biochem 38:1 (2002), 15–25.
103. Gidijala, L., Kiel, J.A., Douma, R.D., Seifar, R.M., van Gulik, W.M., Bovenberg, R.A., et al. An engineered yeast efficiently secreting penicillin. PLoS One, 4(12), 2009, e8317.
104. Kurylenko, O.O., Ruchala, J., Hryniv, O.B., Abbas, C.A., Dmytruk, K.V., Sibirny, A.A., Metabolic engineering and classical selection of the methylotrophic thermotolerant yeast Hansenula polymorpha for improvement of high-temperature xylose alcoholic fermentation. Microb Cell Fact, 13, 2014.
105. Kata, I., Semkiv, M.V., Ruchala, J., Dmytruk, K.V., Sibirny, A.A., Overexpression of the genes PDC1 and ADH1 activates glycerol conversion to ethanol in the thermotolerant yeast Ogataea (Hansenula) polymorpha. Yeast 33:8 (2016), 471–478.
106. Voronovsky, A.Y., Rohulya, O.V., Abbas, C.A., Sibirny, A.A., Development of strains of the thermotolerant yeast Hansenula polymorpha capable of alcoholic fermentation of starch and xylan. Metab Eng 11:4–5 (2009), 234–242.
107. Ryabova, O.B., Chmil, O.M., Sibirny, A.A., Xylose and cellobiose fermentation to ethanol by the thermotolerant methylotrophic yeast Hansenula polymorpha. Fems Yeast Res 4:2 (2003), 157–164.
108. Hong, W.K., Kim, C.H., Heo, S.Y., Luo, L., Oh, B.R., Seo, J.W., Enhanced production of ethanol from glycerol by engineered Hansenula polymorpha expressing pyruvate decarboxylase and aldehyde dehydrogenase genes from Zymomonas mobilis. Biotechnol Lett 32:8 (2010), 1077–1082.
109. Ruchala, J., Kurylenko, O.O., Soontorngun, N., Dmytruk, K.V., Sibirny, A.A., Transcriptional activator Cat8 is involved in regulation of xylose alcoholic fermentation in the thermotolerant yeast Ogataea (Hansenula) polymorpha. Microb Cell Facts, 16, 2017.
110. Macauley-Patrick, S., Fazenda, M.L., McNeil, B., Harvey, L.M., Heterologous protein production using the Pichia pastoris expression system. Yeast 22:4 (2005), 249–270.
111. Jacobs, P.P., Geysens, S., Vervecken, W., Contreras, R., Callewaert, N., Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology. Nat Protoc 4:1 (2009), 58–70.
112. Hamilton, S.R., Gerngross, T.U., Glycosylation engineering in yeast: the advent of fully humanized yeast. Curr Opin Biotechnol 18:5 (2007), 387–392.
113. Hamilton, S.R., Davidson, R.C., Sethuraman, N., Nett, J.H., Jiang, Y.W., Rios, S., et al. Humanization of yeast to produce complex terminally sialylated glycoproteins. Science 313:5792 (2006), 1441–1443.
114. Kavscek, M., Bhutada, G., Madl, T., Natter, K., Optimization of lipid production with a genome-scale model of Yarrowia lipolytica. BMC Syst Biol, 9, 2015.
115. Caspeta, L., Shoaie, S., Agren, R., Nookaew, I., Nielsen, J., Genome-scale metabolic reconstructions of Pichia stipitis and Pichia pastoris and in silico evaluation of their potentials. BMC Syst Biol, 6, 2012.
116. DiCarlo, J.E., Conley, A.J., Penttila, M., Jantti, J., Wang, H.H., Church, G.M., Yeast oligo-mediated genome engineering (YOGE). ACS Synth Biol 2:12 (2013), 741–749.
117. Giaever, G., Nislow, C., The yeast deletion collection: a decade of functional genomics. Genetics 197:2 (2014), 451–465.
118. Shalem, O., Sanjana, N.E., Hartenian, E., Shi, X., Scott, D.A., Mikkelsen, T.S., et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:6166 (2014), 84–87.
119. Wang, T., Wei, J.J., Sabatini, D.M., Lander, E.S., Genetic screens in human cells using the CRISPR-Cas9 system. Science 343:6166 (2014), 80–84.