Skip to main content
SpringerLink
Log in

Transcriptome analysis of the dimorphic transition induced by pH change and lipid biosynthesis in Trichosporon cutaneum

  • Fermentation, Cell Culture and Bioengineering - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Trichosporon cutaneum, a dimorphic oleaginous yeast, has immense biotechnological potential, which can use lignocellulose hydrolysates to accumulate lipids. Our preliminary studies on its dimorphic transition suggested that pH can significantly induce its morphogenesis. However, researches on dimorphic transition correlating with lipid biosynthesis in oleaginous yeasts are still limited. In this study, the unicellular yeast cells induced under pH 6.0–7.0 shake flask cultures resulted in 54.32% lipid content and 21.75 g/L dry cell weight (DCW), so lipid production was over threefold than that in hypha cells induced by acidic condition (pH 3.0–4.0). Furthermore, in bioreactor batch cultivation, the DCW and lipid content in unicellular yeast cells can reach 21.94 g/L and 58.72%, respectively, both of which were also more than twofold than that in hypha cells. Moreover, the activities of isocitrate dehydrogenase (IDH), malic enzyme (MAE), isocitrate lyase (ICL) and ATP citrate lyase (ACL) in unicellular cells were all higher than in the hyphal cells. In the meanwhile, the transcriptome data showed that the genes related to fatty acid biosynthesis, carbon metabolism and encoded Rim101 and cAMP–PKA signaling transduction pathways were significantly up-regulated in unicellular cells, which may play an important role in enhancing the lipid accumulation. In conclusion, our results provided insightful information focused on the molecular mechanism of dimorphic transition and process optimization for enhancing lipid accumulation in T. cutaneum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Alonso-Monge R, Román E, Arana DM, Pla J, Nombela C (2010) Fungi sensing environmental stress. Clin Microbiol Infect 15:17–19

    Google Scholar 

  2. Anderson JJ, Dagley S (1980) Catabolism of aromatic acids in Trichosporon cutaneum. J Bacteriol 141:534–543

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Baek YU, Martin SJ, Davis DA (2006) Evidence for novel pH-dependent regulation of Candida albicans rim101, a direct transcriptional repressor of the cell wall β-glycosidase phr2. Eukaryot Cell 5:1550–1559

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bellou S, Triantaphyllidou IE, Aggeli D, Elazzazy AM, Baeshen MN, Aggelis G (2016) Microbial oils as food additives: recent approaches for improving microbial oil production and its polyunsaturated fatty acid content. Cur Opinin Biotechnol 37:24–35

    CAS  Google Scholar 

  5. Bellou S, Triantaphyllidou IE, Mizerakis P, Aggelis G (2016) High lipid accumulation in Yarrowia lipolytica cultivated under double limitation of nitrogen and magnesium. J Biotechnol 234:116–126

    CAS  PubMed  Google Scholar 

  6. Beopoulos A, Mrozova Z, Thevenieau F, Le Dall MT, Hapala I, Papanikolaou S, Chardot T, Nicaud JM (2008) Control of Lipid Accumulation in the yeast Yarrowia lipolytica. Appl Environ Microbiol 74:7779–7789

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Biswas S, Van Dijck P, Datta A (2007) Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol Mol Biol Rev 71:348–376

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Braga A, Mesquita DP, Amaral AL, Ferreira EC, Belo I (2016) Quantitative image analysis as a tool for Yarrowia lipolytica dimorphic growth evaluation in different culture media. J Biotechnol 217:22–30

    CAS  PubMed  Google Scholar 

  9. Calvey CH, Su YK, Willis LB, McGee M, Jeffries TW (2015) Nitrogen limitation, oxygen limitation, and lipid accumulation in Lipomyces starkeyi. Bioresour Technol 200:780–788

    PubMed  Google Scholar 

  10. Cervantes-Chávez JA, Kronberg F, Passeron S, Ruiz-Herrera J (2009) Regulatory role of the PKA pathway in dimorphism and mating in Yarrowia lipolytica. Fungal Genet Biol 46:390–399

    PubMed  Google Scholar 

  11. Cervantes-Chávez JA, Ruiz-Herrera J (2007) The regulatory subunit of protein kinase a promotes hyphal growth and plays an essential role in Yarrowia lipolytica. FEMS Yeast Res 7:929–940

    PubMed  Google Scholar 

  12. Cervantes-Chávez JA, Ruiz-Herrera J (2006) STE11 disruption reveals the central role of a MAPK pathway in dimorphism and mating in Yarrowia lipolytica. FEMS Yeast Res 6:801–815

    PubMed  Google Scholar 

  13. Chuang LT, Chen DC, Nicaud JM, Madzak C, Chen YH, Huang YS (2010) Co-expression of heterologous desaturase genes in Yarrowia lipolytica. N Biotechnol 27:277–282

    CAS  PubMed  Google Scholar 

  14. Cornet M, Richard ML, Gaillardin C (2009) The homologue of the Saccharomyces cerevisiae rim9, gene is required for ambient pH signalling in Candida albicans. Res Microbiol 160:219–223

    CAS  PubMed  Google Scholar 

  15. Cutler NS, Pan X, Heitman J, Cardenas ME (2001) The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol Biol of Cell 12:4103–4113

    CAS  Google Scholar 

  16. Davis DA (2009) How human pathogenic fungi sense and adapt to pH: the link to virulence. Curr Opin Microbiol 12:365–370

    CAS  PubMed  Google Scholar 

  17. Davis D, Wilson RB, Mitchell AP (2000) Rim101-dependent and-independent pathways govern pH responses in Candida albicans. Mol Cell Biol 20:971–978

    CAS  PubMed  PubMed Central  Google Scholar 

  18. De Lima Barros MB, De Almeida Paes R, Schubach AO (2011) Sporothrix schenckii and Sporotrichosis. Cli microbiol Rev 24:633–654

    Google Scholar 

  19. Du H, Huang G (2016) Environmental pH adaption and morphological transitions in Candida albicans. Curr Genet 62:283–286

    CAS  PubMed  Google Scholar 

  20. Geer BW, Krochko D, Oliver MJ, Walker VK, Williamson JH (1980) A comparative study of the NADP-malic enzymes from drosophila and chick liver. Comp Biochem Physiol 65:25–34

    Google Scholar 

  21. Gerginova M, Zlateva P, Peneva N, Alexieva Z (2014) Influence of phenolic substrates utilised by yeast Trichosporon cutaneum on the degradation kinetics. Biotechnol Biotechnol Equip 281:33–37

    Google Scholar 

  22. Gosling JP, Duggan PF (1971) Activities of tricarboxylic acid cycle enzymes, glyoxylate cycle enzymes, and fructose diphosphatase in bakers’ yeast during adaptation to acetate oxidation. J Bacteriol 106:908–914

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Han TL, Cannon RD, Villasbôas SG (2011) The metabolic basis of Candida albicans morphogenesis and quorum sensing. Fungal Genet Biol 48:747–763

    CAS  PubMed  Google Scholar 

  24. Henne W, Buchkovich N, Emr S (2011) The ESCRT pathway. Dev Cell 21:77–91

    CAS  PubMed  Google Scholar 

  25. Jiang J, Sun YF, Tang X, He CN, Shao YL, Tang YJ, Zhou WW (2017) Alkaline pH shock enhanced production of validamycin A in fermentation of Streptomyces hygroscopicus. Bioresour Technol 249:234–240

    PubMed  Google Scholar 

  26. Karunanithi S, Cullen PJ (2012) The filamentous growth MAPK pathway responds to glucose starvation through the mig1/2 transcriptional repressors in Saccharomyces cerevisiae. Genetics 192:869–887

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Kebaara BW, Langford ML, Navarathna DH, Dumitru R, Nickerson KW, Atkin AL (2008) Candida albicans tup1 is involved in farnesol-mediated inhibition of filamentous-growth induction. Eukaryot Cell 7:980–987

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Kendrick A, Ratledge C (1992) Lipid formation in the oleaginous mould Entomophthora exitalis grown in continuous culture: effects of growth rate, temperature and dissolved oxygen tension on polyunsaturated fatty acids. Appl Microbiol Biotechnol 37:18–22

    CAS  Google Scholar 

  29. Kornberg A (1955) Isocitrate dehydrogenase of yeast (TPN). Methods Enzymol 1:705–709

    CAS  Google Scholar 

  30. Lamb TM, Mitchell AP (2003) The transcription factor rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes nrg1 and smp1 in Saccharomyces cerevisiae. Mol Cell Biol 23:677–686

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lamb TM, Xu W, Diamond A, Mitchell AP (2001) Alkaline response genes of Saccharomyces cerevisiae and their relationship to the RIM101 pathway. J Bio Chem 276:346–353

    Google Scholar 

  32. Lazar Z, Dulermo T, Neuveglise C, Crutz-Le Coq AM, Nicaud JM (2014) Hexokinase-A limiting factor in lipid production from fructose in Yarrowia lipolytica. Metab Eng 26:89–99

    CAS  PubMed  Google Scholar 

  33. Lengeler KB, Davidson RC, D’Souza C, Harashima T, Shen WC, Wang P, Pan X, Waugh M, Heitman J (2000) Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev 64:746–785

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Li M, Martin SJ, Bruno VM, Mitchell AP, Davis DA (2004) Candida albicans rim13p, a protease required for rim101p processing at acidic and alkaline phs. Eukaryot Cell 3:741–751

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Lin ZX, An JY, Wang J, Niu J, Ma C, Wang LB, Yuan GS, Shi LL, Liu LL, Zhang JS, Zhang ZX, Qi J, Lin SZ (2017) Integrated analysis of 454 and Illumina transcriptomic sequencing characterizes carbon flux and energy source for fatty acid synthesis in developing Lindera glauca fruits for woody biodiesel. Biotechnol Biofuels 10:134

    PubMed  PubMed Central  Google Scholar 

  36. Litcher A, Mills D (1997) Fill, a G-protein alpha-subunit that acts upstream of cAMP and is essential for dimorphic switching in haploid cells of Ustilago hordei. Mol Gen Genet 256:426–435

    Google Scholar 

  37. Li Y, Zhao Z, Bai F (2007) High-density cultivation of oleaginous yeast Rhodosporidium toruloides Y4 in fed-batch culture. Enzyme Microb Tech 41:312–317

    Google Scholar 

  38. Li Z, Sun H, Mo X, Li X, Xu B, Tian P (2013) Overexpression of malic enzyme (ME) of Mucor circinelloides improved lipid accumulation in engineered Rhodotorula glutinis. Appl Microbiol Biotechnol 97:4927–4936

    CAS  PubMed  Google Scholar 

  39. Martínezespinoza AD, Ruizherrera J, Leónramírez CG, Gold SE (2004) Map kinase and camp signaling pathways modulate the pH-induced yeast-to-mycelium dimorphic transition in the corn smut fungus Ustilago maydis. Curr Microbiol 49:274–281

    Google Scholar 

  40. Miller GL (1959) Use of dinitrosalicylic acid reagent for determination of reducing sugar. Anal Chem 31:426–428

    CAS  Google Scholar 

  41. Murad AMA, D’Enfert C, Gaillardin C, Tournu H, Tekaia F, Talibi D, Marechal D, Marchais V, Cottin J, Brown AJP (2001) Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1. Mol Microbiol 42:981–993

    CAS  PubMed  Google Scholar 

  42. O’Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, Alspaugh JA (2010) Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog 6:e1000776

    PubMed  PubMed Central  Google Scholar 

  43. Patel A, Pruthi V, Singh RP, Pruthi PA (2015) Synergistic effect of fermentable and non-fermentable carbon sources enhances TAG accumulation in oleaginous yeast Rhodosporidium kratochvilovae HIMPA1. Bioresour Technol 188:136–144

    CAS  PubMed  Google Scholar 

  44. Qiao K, Imam Abidi SH, Liu H, Zhang H, Chakraborty S, Watson N, Kumaran Ajikumar P, Stephanopoulos G (2015) Engineering lipid overproduction in the oleaginous yeast Yarrowia lipolytica. Metab Eng 29:56–65

    CAS  PubMed  Google Scholar 

  45. Runguphan W, Keasling JD (2014) Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals. Metab Eng 21:103–113

    CAS  PubMed  Google Scholar 

  46. Sakarika M, Kornaros M (2016) Effect of pH on growth and lipid accumulation kinetics of the microalga Chlorella vulgaris, grown heterotrophically under sulfur limitation. Bioresour Technol 219:694–701

    CAS  PubMed  Google Scholar 

  47. Sang MN (2011) Cephalosporin C fermentation performance under different ammonium sulfate and soybean oil feeding strategies. Chin J Biotech 38:1321–1330

    CAS  Google Scholar 

  48. Saporito-Irwin SM, Birse CE, Sypherd PS, Fonzi WA (1995) PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis. Mol Cell Biol 15:601–613

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Sieńko M, Stępień PP, Paszewski A (1992) Generation of genetic recombinants in Trichosporon cutaneum by spontaneous segregation of protoplast fusants. J Gen Microbiol 138:1409–1412

    PubMed  Google Scholar 

  50. Smith DG, Garcia-Pedrajas MD, Garcia-Pedrajas SE, Perlin MH (2003) Isolation and characterization from pathogenic fungi of genes encoding ammonium permeases and their roles in dimorphism. Mol Microbiol 50:259–275

    CAS  PubMed  Google Scholar 

  51. Smith RL, Johnson AD (2000) Turning genes off by Ssn6–Tup1: a conserved system of transcriptional repression in eukaryotes. Trends Biochem Sci 25:325–330

    CAS  PubMed  Google Scholar 

  52. Srere PA (1959) The citrate cleavage enzyme. I. Distribution and purification. J Biol Chem 234:2544–2547

    CAS  PubMed  Google Scholar 

  53. Sun Q, Chen X, Ren X, Zheng G, Mao Z (2015) Enhanced ε-poly-l-lysine production through pH regulation and organic nitrogen addition in fed-batch fermentation. Chin J Biotechnol 31:752–756

    Google Scholar 

  54. 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

    CAS  PubMed  Google Scholar 

  55. Thevelein JM, De Winde JH (1999) Novel sensing mechanisms and targets for the cAMP—protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 33:904–918

    CAS  PubMed  Google Scholar 

  56. Timoumi A, Cléret M, Bideaux C, Guillouet SE, Allouche Y, Molina-Jouve C, Fillaudeau L, Gorret N (2017) Dynamic behavior of Yarrowia lipolytica in response to pH perturbations: dependence of the stress response on the culture mode. Appl Microbiol Biotechnol 101:351–366

    CAS  PubMed  Google Scholar 

  57. Timoumi A, Guillouet SE, Molina-Jouve C, Fillaudeau L, Gorret N (2018) Impacts of environmental conditions on product formation and morphology of Yarrowia lipolytica. Appl Microbiol Biotechnol 102:3831–3848

    CAS  PubMed  Google Scholar 

  58. Yuan J, Ai Z, Zhang Z, Yan R, Zeng Q, Zhu D (2011) Microbial oil production by Trichosporon cutaneum B3 using cassava starch. Chin J Biotechnol 27:453–460

    CAS  Google Scholar 

  59. Zakikhany K, Naglik JR, Schmidt-Westhausen A, Holland G, Schaller M, Hube B (2007) In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell Microbiol 9:2938–2954

    CAS  PubMed  Google Scholar 

  60. Zhang H, Zhang L, Chen H, Chen YQ, Chen W, Song Y, Ratledge C (2014) Enhanced lipid accumulation in the yeast Yarrowia lipolytica by over-expression of ATP: citrate lyase from Mus musculus. J Biotechnol 192:78–84

    CAS  PubMed  Google Scholar 

  61. Zhu LB, Wang Y, Zhang ZB, Yang HL, Yan RM, Zhu D (2017) Influence of environmental and nutritional conditions on yeast-mycelial dimorphic transition in Trichosporon cutaneum. Biotechnol Biotechnol Equip 31:516–526

    CAS  Google Scholar 

  62. Zhu Z, Zhang S, Liu H, Shen H, Lin X, Yang F, Zhou YJ, Jin G, Ye M, Zou H, Zhao ZK (2012) A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides. Nat Commun 3:1112

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 31760021, 21466015), the Jiangxi Provincial Science Foundation for Distinguished Young Scholars (20171BCB23037), the Foundation of Jiangxi Provincial Department of Education (No. GJJ160310) and Jiangxi Provincial Department of Education for Technological Innovations.

Author information

Author notes

  1. Ya Wang and Li Juan Tang contributed equally to this work.

Authors and Affiliations

  1. College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang, 330013, China

    Ya Wang & Du Zhu

  2. Key Laboratory of Protection and Utilization of Subtropic Plant Resources of Jiangxi Province, Jiangxi Normal University, Nanchang, 330022, China

    Li Juan Tang, Xuan Peng, Zhi Bin Zhang, Hui Lin Yang, Ri Ming Yan & Du Zhu

  3. State Key Laboratory of Microbial Metabolism & School of Life Science and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai, 200240, China

    Ya Wang

Authors
  1. Ya Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Juan Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuan Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi Bin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Lin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ri Ming Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Du Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Du Zhu.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 309 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Tang, L.J., Peng, X. et al. Transcriptome analysis of the dimorphic transition induced by pH change and lipid biosynthesis in Trichosporon cutaneum. J Ind Microbiol Biotechnol 47, 49–61 (2020). https://doi.org/10.1007/s10295-019-02244-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-019-02244-9

Keywords

Search

Navigation