Skip to main content
SpringerLink
Log in

Ceramide’s Role and Biosynthesis: A Brief Review

  • Review Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

The utilization of ceramides, which are members of the sphingolipid family, has been widely acknowledged in the cosmetic and pharmaceutical industries, along with various other applications as therapeutic agents. Most ceramides currently available on the market are synthetic ceramides created through chemical reactions with precursors resembling the natural precursor of sphingolipid production by living organisms. In fact, many organisms ranging from microbes to higher-order mammals natively use metabolism to produce sphingolipids, including ceramides and their derivatives, to support cell molecular functions. Sphingolipids, for instance, are present in the cell membranes of mammals, plants, and yeast to maintain membrane morphology. As a green alternative to the chemical synthesis method, many studies have been carried out to reveal the diversity and characteristics of biologically produced ceramide derivatives. In this review, we summarized the most important aspects of ceramide biosynthesis in general and provide a quick overview of the common organisms producing ceramides. In addition, a brief discussion regarding the role of ceramides in cells and their risks was included. As the biosynthesis of ceramides is an attractive alternative to current commercial methods, the advances reviewed herein demonstrate the untapped potential for the further development of synthetic pathways to enhance biobased-ceramide production.

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

Similar content being viewed by others

References

  1. Engelking, L. R. (2015) Textbook of Veterinary Physiological Chemistry. 3rd ed., pp. 378–383. Academic Press.

  2. Merrill, A. H., Jr. (2008) Sphingolipids. pp. 363–397. In: D. E. Vance and J. E. Vance (eds.). Biochemistry of Lipids, Lipoproteins and Membranes. 5th ed. Elsevier Science.

  3. Murakami, S., T. Shimamoto, H. Nagano, M. Tsuruno, H. Okuhara, H. Hatanaka, H. Tojo, Y. Kodama, and K. Funato (2015) Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae. Sci. Rep. 5: 16319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Holleran, W. M., Y. Takagi, and Y. Uchida (2006) Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett. 580: 5456–5466.

    Article  CAS  PubMed  Google Scholar 

  5. Nishifuji, K. and J. S. Yoon (2013) The stratum corneum: the rampart of the mammalian body. Vet. Dermatol. 24: 60–72.sme15–72.e16.

    Article  PubMed  Google Scholar 

  6. Kim, D.-S., S.-Y. Kim, J.-H. Chung, K.-H. Kim, H.-C. Eun, and K.-C. Park (2002) Delayed ERK activation by ceramide reduces melanin synthesis in human melanocytes. Cell. Signal. 14: 779–785.

    Article  CAS  PubMed  Google Scholar 

  7. Coderch, L., O. López, A. de la Maza, and J. L. Parra (2003) Ceramides and skin function. Am. J. Clin. Dermatol. 4: 107–129.

    Article  PubMed  Google Scholar 

  8. Sajna, K. V., L. D. Gottumukkala, R. K. Sukumaran, and A. Pandey (2015) White biotechnology in cosmetics. pp. 607–652. In: A. Pandey, R. Höfer, M. Taherzadeh, K. M. Nampoothiri, and C. Larroche (eds.). Industrial Biorefineries and White Biotechnology. Elsevier.

  9. Becam, J., T. Walter, A. Burgert, J. Schlegel, M. Sauer, J. Seibel, and A. Schubert-Unkmeir (2017) Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria. Sci. Rep. 7: 17627.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wolf, H.-U. (2015) Ceramide dimers and use thereof as pharmaceutical preparation or cosmetic preparation. US Patent 9,018,405.

  11. Nayak, R., I. Meerovich, and A. K. Dash (2019) Translational multi-disciplinary approach for the drug and gene delivery systems for cancer treatment. AAPS PharmSciTech 20: 160.

    Article  PubMed  Google Scholar 

  12. Zeidan, Y. H., R. W. Jenkins, and Y. A. Hannun (2008) Remodeling of cellular cytoskeleton by the acid sphingomyelinase/ceramide pathway. J. Cell Biol. 181: 335–350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yang, L., L. Zheng, Y. Tian, Z. Zhang, W. Dong, X. Wang, X. Zhang, and C. Cao (2015) C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: a mechanism study. Exp. Cell Res. 332: 47–59.

    Article  CAS  PubMed  Google Scholar 

  14. Venkataramana, S. H., N. Puttaswamy, and S. Kodimule (2020) Potential benefits of oral administration of AMORPHOPHALLUS KONJAC glycosylceramides on skin health - a randomized clinical study. BMC Complement. Med. Ther. 20: 26.

    Article  Google Scholar 

  15. Ohta, K., S. Hiraki, M. Miyanabe, T. Ueki, K. Aida, Y. Manabe, and T. Sugawara (2021) Appearance of intact molecules of dietary ceramides prepared from soy sauce lees and rice glucosylceramides in mouse plasma. J. Agric. Food Chem. 69: 9188–9198.

    Article  CAS  PubMed  Google Scholar 

  16. Tsuchiya, Y., M. Ban, M. Kishi, T. Ono, and H. Masaki (2020) Safety and efficacy of oral intake of ceramide-containing acetic acid bacteria for improving the stratum corneum hydration: a randomized, double-blind, placebo-controlled study over 12 weeks. J. Oleo Sci. 69: 1497–1508.

    Article  CAS  PubMed  Google Scholar 

  17. Cha, H. J., C. He, H. Zhao, Y. Dong, I. S. An, and S. An (2016) Intercellular and intracellular functions of ceramides and their metabolites in skin. Int. J. Mol. Med. 38: 16–22.

    Article  CAS  PubMed  Google Scholar 

  18. Abbas, H. K., T. Tanaka, S. O. Duke, J. K. Porter, E. M. Wray, L. Hodges, A. E. Sessions, E. Wang, A. H. Merrill Jr., and R. T. Riley (1994) Fumonisin- and AAL-toxin-induced disruption of sphingolipid metabolism with accumulation of free sphingoid bases. Plant Physiol. 106: 1085–1093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bionda, C., J. Portoukalian, D. Schmitt, C. Rodriguez-Lafrasse, and D. Ardail (2004) Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and/or mitochondria? Biochem. J. 382: 527–533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Eisenberg, T. and S. Büttner (2014) Lipids and cell death in yeast. FEMS Yeast Res. 14: 179–197.

    Article  CAS  PubMed  Google Scholar 

  21. Berkey, R., D. Bendigeri, and S. Xiao (2012) Sphingolipids and plant defense/disease: the “death” connection and beyond. Front. Plant Sci. 3: 68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hwang, J., B. G. Peterson, J. Knupp, and R. D. Baldridge (2023) The ERAD system is restricted by elevated ceramides. Sci. Adv. 9: eadd8579.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Raichur, S. (2020) Ceramide synthases are attractive drug targets for treating metabolic diseases. Front. Endocrinol. (Lausanne) 11: 483.

    Article  PubMed  Google Scholar 

  24. Levy, M. and A. H. Futerman (2010) Mammalian ceramide synthases. IUBMB Life 62: 347–356.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Mullen, T. D., Y. A. Hannun, and L. M. Obeid (2012) Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem. J. 441: 789–802.

    Article  CAS  PubMed  Google Scholar 

  26. Mizushima, H., J. I. Fukasawa, and T. Suzuki (1996) Phase behavior of artificial stratum corneum lipids containing a synthetic pseudo-ceramide: a study of the function of cholesterol. J. Lipid Res. 37: 361–367.

    Article  CAS  PubMed  Google Scholar 

  27. Markham, J. E., D. V. Lynch, J. A. Napier, T. M. Dunn, and E. B. Cahoon (2013) Plant sphingolipids: function follows form. Curr. Opin. Plant Biol. 16: 350–357.

    Article  CAS  PubMed  Google Scholar 

  28. Tessema, E. N., T. Gebre-Mariam, R. H. H. Neubert, and J. Wohlrab (2017) Potential applications of phyto-derived ceramides in improving epidermal barrier function. Skin Pharmacol. Physiol. 30: 115–138.

    Article  CAS  PubMed  Google Scholar 

  29. Lynch, D. V. and T. M. Dunn (2004) An introduction to plant sphingolipids and a review of recent advances in understanding their metabolism and function. New Phytol. 161: 677–702.

    Article  CAS  PubMed  Google Scholar 

  30. Warnecke, D. and E. Heinz (2003) Recently discovered functions of glucosylceramides in plants and fungi. Cell. Mol. Life Sci. 60: 919–941.

    Article  CAS  PubMed  Google Scholar 

  31. Börgel, D., M. van den Berg, T. Hüller, H. Andrea, G. Liebisch, E. Boles, C. Schorsch, R. van der Pol, A. Arink, I. Boogers, R. van der Hoeven, K. Korevaar, M. Farwick, T. Köhler, and S. Schaffer (2012) Metabolic engineering of the non-conventional yeast Pichia ciferrii for production of rare sphingoid bases. Metab. Eng. 14: 412–426.

    Article  PubMed  Google Scholar 

  32. Schaffer, S., M. A. Van Den Berg, D. Boergel, and T. Hueller (2013) Method for obtaining a microbial strain for production of sphingoid bases. US Patent 8,372,595.

  33. Han, C., M. Jang, M. J. Kim, M.-H. Han, K.-R. Lee, J.-S. Hahn, and J. Ahn (2021) Engineering Yarrowia lipolytica for de novo production of tetraacetyl phytosphingosine. J. Appl. Microbiol. 130: 1981–1992.

    Article  CAS  PubMed  Google Scholar 

  34. Choi, J. Y., H. J. Hwang, W. Y. Cho, J. I. Choi, and P. C. Lee (2021) Differences in the fatty acid profile, morphology, and tetraacetylphytosphingosine-forming capability between wild-type and mutant Wickerhamomyces ciferrii. Front. Bioeng. Biotechnol. 9: 662979.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Park, S.-B., Q.-G. Tran, A. J. Ryu, J.-H. Yun, K. K. Kwon, Y. J. Lee, and H.-S. Kim (2022) Fluorescence-activated cell sorting-mediated directed evolution of Wickerhamomyces ciferrii for enhanced production of tetraacetyl phytosphingosine. Korean J. Chem. Eng. 39: 1004–1010.

    Article  CAS  Google Scholar 

  36. Kwun, K. H., J. Lee, K. Rho, and H. Yun (2006) Production of ceramide with Saccharomyces cerevisiae. Appl. Biochem. Biotechnol. 133: 203–210.

    Article  CAS  PubMed  Google Scholar 

  37. Olea-Ozuna, R. J., S. Poggio, EdBergström, E. Quiroz-Rocha, D. A. García-Soriano, D. X. Sahonero-Canavesi, J. Padilla-Gómez, L. Martínez-Aguilar, I. M. López-Lara, J. Thomas-Oates, and O. Geiger (2021) Five structural genes required for ceramide synthesis in Caulobacter and for bacterial survival. Environ. Microbiol. 23: 143–159.

    Article  CAS  PubMed  Google Scholar 

  38. Brown, E. M., X. Ke, D. Hitchcock, S. Jeanfavre, J. Avila-Pacheco, T. Nakata, T. D. Arthur, N. Fornelos, C. Heim, E. A. Franzosa, N. Watson, C. Huttenhower, H. J. Haiser, G. Dillow, D. B. Graham, B. B. Finlay, A. D. Kostic, J. A. Porter, H. Vlamakis, C. B. Clish, and R. J. Xavier (2019) Bacteroides-derived sphingolipids are critical for maintaining intestinal homeostasis and symbiosis. Cell Host Microbe 25: 668–680.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Stankeviciute, G., P. Tang, B. Ashley, J. D. Chamberlain, M. E. B. Hansen, A. Coleman, R. D’Emilia, L. Fu, E. C. Mohan, H. Nguyen, Z. Guan, D. J. Campopiano, and E. A. Klein (2022) Convergent evolution of bacterial ceramide synthesis. Nat. Chem. Biol. 18: 305–312.

    Article  CAS  PubMed  Google Scholar 

  40. Hammarström, S. (1971) A convenient procedure for the synthesis of ceramides. J. Lipid Res. 12: 760–765.

    Article  PubMed  Google Scholar 

  41. Bergfeld, W. F., D. V. Belsito, R. A. Hill, C. D. Klaassen, D. C. Liebler, J. G. Marks Jr., R. C. Shank, T. J. Slaga, and P. W. Snyder (2015) Safety Assessment of Ceramides as Used in Cosmetics. Cosmetic Ingredient Review.

  42. Schorsch, C., T. Köhler, H. Andrea, and E. Boles (2012) Highlevel production of tetraacetyl phytosphingosine (TAPS) by combined genetic engineering of sphingoid base biosynthesis and L-serine availability in the non-conventional yeast Pichia ciferrii. Metab. Eng. 14: 172–184.

    Article  CAS  PubMed  Google Scholar 

  43. Casey, J., P. S. J. Cheetham, P. C. Harries, D. Hyliands, J. T. Mitchell, and A. V. Rawlings (1998) Method of synthesising phytosphingosine-containing ceramides and cosmetic compositions comprising them. European Patent EP0667853.

  44. Flor-Parra, I., S. Sabido-Bozo, A. Ikeda, K. Hanaoka, A. Aguilera-Romero, K. Funato, M. Muñiz, and R. Lucena (2021) The ceramide synthase subunit Lac1 regulates cell growth and size in fission yeast. Int. J. Mol. Sci. 23: 303.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Liu, N. J., L. P. Hou, J. J. Bao, L. J. Wang, and X. Y. Chen (2021) Sphingolipid metabolism, transport, and functions in plants: recent progress and future perspectives. Plant Commun. 2: 100214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Markham, J. E. and J. G. Jaworski (2007) Rapid measurement of sphingolipids from Arabidopsis thaliana by reversed-phase high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. Rapid Commun. Mass Spectrom. 21: 1304–1314.

    Article  CAS  PubMed  Google Scholar 

  47. Tarazona, P., K. Feussner, and I. Feussner (2015) An enhanced plant lipidomics method based on multiplexed liquid chromatographymass spectrometry reveals additional insights into cold- and drought-induced membrane remodeling. Plant J. 84: 621–633.

    Article  CAS  PubMed  Google Scholar 

  48. Ishikawa, T., L. Fang, E. A. Rennie, J. Sechet, J. Yan, B. Jing, W. Moore, E. B. Cahoon, H. V. Scheller, M. Kawai-Yamada, and J. C. Mortimer (2018) GLUCOSAMINE INOSITOLPHOSPHORYLCERAMIDE TRANSFERASE1 (GINT1) is a GlcNAc-containing glycosylinositol phosphorylceramide glycosyltransferase. Plant Physiol. 177: 938–952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cacas, J.-L., C. Buré, K. Grosjean, P. Gerbeau-Pissot, J. Lherminier, Y. Rombouts, E. Maes, C. Bossard, J. Gronnier, F. Furt, L. Fouillen, V. Germain, E. Bayer, S. Cluzet, F. Robert, J.-M. Schmitter, M. Deleu, L. Lins, F. Simon-Plas, and S. Mongrand (2016) Revisiting plant plasma membrane lipids in tobacco: a focus on sphingolipids. Plant Physiol. 170: 367–384.

    Article  CAS  PubMed  Google Scholar 

  50. Cacas, J.-L., C. Buré, F. Furt, J.-P. Maalouf, A. Badoc, S. Cluzet, J.-M. Schmitter, E. Antajan, and S. Mongrand (2013) Biochemical survey of the polar head of plant glycosylinositolphosphoceramides unravels broad diversity. Phytochemistry 96: 191–200.

    Article  CAS  PubMed  Google Scholar 

  51. Ngo, T. N., N. D. P. Nguyen, N. T. L. Nguyen, N. K. T. Pham, N. M. Phan, T. D. Bui, V. S. Dang, C. L. Tran, D. T. Mai, and T. P. Nguyen (2020) Markhasphingolipid A, new phytosphingolipid from the leaves of Markhamia stipulata var. canaense V.S. Dang. Nat. Prod. Res. 34: 1820–1826.

    Article  CAS  PubMed  Google Scholar 

  52. Petschnigg, J., H. Wolinski, D. Kolb, G. Zellnig, C. F. Kurat, K. Natter, and S. D. Kohlwein (2009) Good fat, essential cellular requirements for triacylglycerol synthesis to maintain membrane homeostasis in yeast. J. Biol. Chem. 284: 30981–30993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This review was supported by grants from the National Science and Technology Council, Taiwan (MOST-109-2628-E-011 -001 -MY3).

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan

    Lita Amalia & Shen-Long Tsai

Authors
  1. Lita Amalia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shen-Long Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shen-Long Tsai.

Ethics declarations

The authors declare there is no conflict of interest. Neither ethical approval nor informed consent was required for this study.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amalia, L., Tsai, SL. Ceramide’s Role and Biosynthesis: A Brief Review. Biotechnol Bioproc E 28, 371–378 (2023). https://doi.org/10.1007/s12257-022-0257-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-022-0257-8

Keywords

Search

Navigation