Skip to main content
SpringerLink
Log in

Efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with high substrate concentration and product yield

  • Biotechnological products and process engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

A new two-step chemo-enzymatic approach for highly efficient synthesis of all-trans-retinyl palmitate is constructed in this study. In the first step, retinyl acetate as starting material was fully hydrolyzed to retinol by potassium hydroxide. In the hydrolysis system, anhydrous ethanol was the best co-solvent to increase the solubility of retinyl acetate. The addition amounts of 5 M potassium hydroxide and anhydrous ethanol were 8 and 10 mL against 10 g retinyl acetate, respectively, and 100 % hydrolysis rate was obtained. In the second step, esterification was catalyzed by immobilized lipase on macroporous acrylic resin AB-8 using the extracted retinol and palmitic acid as substrates in non-aqueous system. After optimization, the parameters of esterification reaction were confirmed as follows: non-aqueous solvent was selected as n-hexane, washing times of extraction solution was four times, retinol concentration was 300 g/L, substrate molar ratio of retinol to palmitic acid was 1:1.1, the amount of immobilized enzyme was 10 g/L, and the esterification temperature was 30 °C. Under the optimal conditions, this protocol resulted in a 97.5 % yield of all-trans-retinyl palmitate in 700-L reactor. After purification, all-trans-retinyl palmitate was obtained with above 99 % of purity and 88 % of total recovery rate. This methodology provides a promising strategy for the large-scale production of all-trans-retinyl palmitate.

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adlercreutz P (2013) Immobilisation and application of lipases in organic media. Chem Soc Rev 42(15):6406–6436

    Article  CAS  PubMed  Google Scholar 

  • Ajima A, Takahashi K, Matsushima A, Saito Y, Inada Y (1986) Retinyl esters synthesis by polyethylene glycol-modified lipase in benzene. Biotechnol Lett 8(8):547–552

    Article  CAS  Google Scholar 

  • Blondel JCRG, Fouche JCL (1970) Phenthiazine derivatives. US Patent 3 627 759

  • Chen HC (2011) Optimization of ultrasound-accelerated synthesis of enzymatic caffeic acid phenethyl ester by response surface methodology. Ultrason Sonochem 18(1):455–459

    Article  CAS  PubMed  Google Scholar 

  • Corey J, Dorogi PL, Meyers AJ, V. A (1999) Cosmetic composition with a retinol fatty acid ester. US Patent 5 885 595

  • Courraud J, Berger J, Cristol JP, Avallone S (2013) Stability and bioaccessibility of different forms of carotenoids and vitamin A during in vitro digestion. Food Chem 136(2):871–877

    Article  CAS  PubMed  Google Scholar 

  • Dong H, Li Y, Sheng G, Hu L (2013) The study on effective immobilization of lipase on functionalized bentonites and their properties. J Mol Catal B Enzym 95(11):9–15

    Article  CAS  Google Scholar 

  • Duell EA, Kang S, Voorhess JJ (1997) Unoccluded retinol penetrates human skin in vivo more effectively than unoccluded retinyl palmitate or retinoic acid. J Invest Dermatol 109(3):301–305

    Article  CAS  PubMed  Google Scholar 

  • Freitas L, Bueno T, Perez VH, Santos JC, Castro HFD (2007) Enzymatic hydrolysis of soybean oil using lipase from different sources to yield concentrated of polyunsaturated fatty acids. World J Microb Biotechnol 23(12):1725–1731

    Article  CAS  Google Scholar 

  • Gaspar LR, Campos PM (2007) Photostability and efficacy studies of topical formulations containing UV-filters combination and vitamins A, C and E. Int J Pharm 343(1):181–189

    Article  CAS  PubMed  Google Scholar 

  • Gerster H (1997) Vitamin A—functions, dietary requirements and safety in humans. Int J Vitam Nutr Res 67(2):71–90

    CAS  PubMed  Google Scholar 

  • Gustafsson H (2013) Enzyme immobilization in mesoporous silica. Dissertation, Chalmers University of Technology

  • Ha SH, Anh TV, Lee SH, Koo YM (2012) Effect of ionic liquids on enzymatic synthesis of caffeic acid phenethyl ester. Bioprocess Biosyst Eng 35(1-2):235–240

    Article  CAS  PubMed  Google Scholar 

  • Hanefeld U, Gardossi L, Magner E (2009) Understanding enzyme immobilisation. Chem Soc Rev 38(2):453–468

    Article  CAS  PubMed  Google Scholar 

  • Janz GJ, Wait SC (1955) Space-time yield and reaction rate. J Chem Phys 23(8):1550–1551

    Article  CAS  Google Scholar 

  • Karmee SK (2009) Biocatalytic synthesis of ascorbyl esters and their biotechnological applications. Appl Microbiol Biotechnol 81(6):1013–1022

    Article  CAS  PubMed  Google Scholar 

  • Liu ZQ, Zheng XB, Zhang SP, Zheng YG (2012) Cloning, expression and characterization of a lipase gene from the Candida antarctica ZJB09193 and its application in biosynthesis of vitamin A esters. Microbiol Res 167(8):452–460

    Article  CAS  PubMed  Google Scholar 

  • Lousa D, Baptista AM, Soares CM (2013) A molecular perspective on nonaqueous biocatalysis: contributions from simulation studies. Phys Chem Chem Phys 15(33):13723–13736

    Article  CAS  PubMed  Google Scholar 

  • Mateo C, Palomo JM, Fernandez LG, Guisan JM, Fernandez LR (2007) Improvement of enzyme activity, stability and selectivity via immobilization techniques. Enzyme Microb Technol 40(6):1451–1463

    Article  CAS  Google Scholar 

  • Mitsutaka T, Tadashi H, Kunio T (1994) Process for producing vitamin A derivatives. US Patent 5 424 478

  • Moreno PS, Filice M, Guisan JM (2013) Synthesis of ascorbyl oleate by transesterification of olive oil with ascorbic acid in polar organic media catalyzed by immobilized lipases. Chem Phys Lipids 174(3):48–54

    Article  Google Scholar 

  • Patrick A (2013) Immobilisation and application of lipases in organic media. Chem Soc Rev 42(15):6406–6436

    Article  Google Scholar 

  • Pommer H, Thieme P (1983) Industrial applications of the wittig reaction. Top Curr Chem 109(4):165–188

    Article  CAS  Google Scholar 

  • Poppe JK, Garcia GC, Matte CR, Fernandez LR, Rodrigues RC, Ayub MAZ (2013) Optimization of synthesis of fatty acid methyl esters catalyzed by lipase B from Candida antarctica immobilized on hydrophobic supports. J Mol Catal B Enzym 94(10):51–56

    Article  CAS  Google Scholar 

  • Prat D, Hayler J, Wells A (2014) A survey of solvent selection guides. Green Chem 16(10):4546–4551

    Article  CAS  Google Scholar 

  • Rejasse B, Maugard T, Legoy MD (2003) Enzymatic procedures for the synthesis of water-soluble retinol derivatives in organic media. Enzyme Microb Technol 32(2):312–320

    Article  CAS  Google Scholar 

  • Riaz MN, Asif M, Ali R (2009) Stability of vitamins during extrusion. Crit Rev Food Sci 49(4):361–368

    Article  CAS  Google Scholar 

  • Rodrigues RC, Ortiz C, Berenguer MA, Torres R, Fernández LR (2013) Modifying enzyme activity and selectivity by immobilization. Chem Soc Rev 42(15):6290–6307

    Article  CAS  PubMed  Google Scholar 

  • Semba RD (1998) The role of vitamin A and related retinoids in immune function. Nutr Rev 56(1):S38–S48

    Article  CAS  PubMed  Google Scholar 

  • Stergiou PY, Foukis A, Filippou M, Koukouritaki M, Parapouli M, Theodorou LG, Hatziloukas E, Afendra A, Pandey A, Papamichael EM (2013) Advances in lipase-catalyzed esterification reactions. Biotechnol Adv 31(8):1846–1859

    Article  CAS  PubMed  Google Scholar 

  • Toshiya T, Shinzo S (2001) Dihalo-compound and process for producing vitamin A derivative. US Patent 6 388 124

  • Tung KH, Wilkens LR, Wu AH, McDuffie K, Hankin JH, Nomura AMY, Kolonel LN, Goodman MT (2005) Association of dietary vitamin A, carotenoids, and other antioxidants with the risk of ovarian cancer. Cancer Epidemiol Biomarkers Prev 14(3):669–676

    Article  CAS  PubMed  Google Scholar 

  • Wang ZG, Wang JQ, Xu ZK (2006) Immobilization of lipase from Candida rugosa on electrospun polysulfone nanofibrous membranes by adsorption. J Mol Catal B Enzym 42(1):45–51

    Article  Google Scholar 

  • Wojtal KA, Wolfram L, Frey-Wagner I, Lang S, Scharl M, Vavricka SR, Rogler G (2013) The effects of vitamin A on cells of innate immunity in vitro. Toxicol in Vitro 27(5):1525–1532

    Article  CAS  PubMed  Google Scholar 

  • Yadav GD, Devendran S (2012) Lipase catalyzed synthesis of cinnamyl acetate via transesterification in non-aqueous medium. Process Biochem 47(3):496–502

    Article  CAS  Google Scholar 

  • Yin CH, Liu T, Tan TW (2006) Synthesis of vitamin A esters by immobilized Candida sp. lipase in organic media. Chin J Chem Eng 14(1):81–86

    Article  CAS  Google Scholar 

  • Zhu K, Wang JQ, Wang YH, Liu H, Han PF, Wei P (2011) Synthesis of retinyl palmitate catalyzed by Candida sp.99-125 lipase immobilized on fiber-like SBA-15 mesoporous material. J Nanosci Nanotechnol 11(9):7593–7602

    Article  CAS  Google Scholar 

  • Zor T, Selinger Z (1996) Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies. Anal Biochem 236(2):302–308

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no financial or non-financial conflict of interest in the publication of this manuscript.

Author information

Authors and Affiliations

  1. Institute of Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Zhi-Qiang Liu, Ling-Mei Zhou, Peng Liu, Peter James Baker, Shan-Shan Liu, Ya-Ping Xue & Yu-Guo Zheng

  2. Zhejiang Laiyi Biotechnology Co. Ltd., Shengzhou, Zhejiang, 312400, People’s Republic of China

    Ming Xu

Authors
  1. Zhi-Qiang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling-Mei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter James Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shan-Shan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ya-Ping Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu-Guo Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu-Guo Zheng.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 1065 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, ZQ., Zhou, LM., Liu, P. et al. Efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with high substrate concentration and product yield. Appl Microbiol Biotechnol 99, 8891–8902 (2015). https://doi.org/10.1007/s00253-015-6825-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-015-6825-5

Keywords

Search

Navigation