Introduction

HMFS is one kind of structured lipids designed to resemble triacylglycerols (TAGs) in HMF in terms of fatty acid composition and distribution. It not only provides 40–55% of the dietary energy and essential fatty acids, but also helps the absorption of other nutrients, the development of brain and so on [1, 2]. However, the compositions of triacylglycerols in vegetable oils differ greatly from those contained in HMF. High palmitic acid (PA, C16:0) content at sn-1,3 positions will lead to the formation of calcium soap, further cause loss of minerals, constipation, abdominal pain and intestinal blockage [3, 4]. Therefore, the preparation of HMFS with high similarity to HMF has received extensive attention.

It is recognized that HMF contains more than two hundred kinds of fatty acids, in which palmitic acid (20–30%), oleic acid (OA, C18:1) (25–40%) and linoleic acid (LA, C18:2) (10–30%) are the most abundant [2, 4,5,6]. About 60–70% palmitic acid is esterified at sn-2 position, whereas sn-1,3 positions are mainly occupied by unsaturated fatty acids. This profile corresponds to the digestive characteristics of infants, thus can ensures proper absorption of lipids and other nutrients. Besides these long chain fatty acids (LCFAs), medium chain fatty acids (MCFAs) and long chain polyunsaturated fatty acids (PUFAs) also have a positive impact on infant development, although their contents are usually lower than 1% [7, 8]. Medium chain fatty acids tend to be distributed on the glycerol backbone together with long chain fatty acids, mainly in the form of medium- and long-chain triglycerides (MLCTs) [9, 10]. It should be noted that both the composition and distribution of fatty acids have a valuable function for infants. Mimicking such complex compositions and unique structures is a major challenge in HMFS synthesis.

Due to the mild reaction conditions and high selectivity of enzymes, lipase-mediated preparation of HMFS is preferred and has been drawing increasing interest in recent years [4, 11]. The selectivity of lipase makes it possible to synthesize HMFS with desirable fatty acid composition and distribution. Apart from enzyme itself, different enzymatic synthetic route as well as the reaction medium and acyl migration have been demonstrated to play a significant role in the preparation of HMFS. In this review, the related progress and the perspective of lipase-mediated production of HMFS are presented.

Different enzymatic approaches for HMFS production

Enzymatic production of HMFS can be classified as one-step, two-step and multiple-step process, and different approach has its own merits and challenges as elaborated below.

One-step acidolysis/transesterification process

Enzymatic one-step process for HMFS synthesis mainly comprises one-step acidolysis or one-step transesterification [3, 4, 12]. The acidolysis reaction is generally carried out between triacylglycerols (tripalmitin (PPP) or oil/fat rich in palmitic acid/medium chain fatty acids at sn-2 position) with free fatty acids (FFAs) (generally LCFAs, such as oleic acid, linoleic acid and polyunsaturated fatty acids), and the typical reaction is shown in Fig. 1. This one-step acidolysis reaction has been widely used for the synthesis of various types of HMFS and in terms of the types of HMFS, one-step acidolysis has been adopted for the production of 1-oleoyl-2-palmitoyl-3-oleoylglycerol (OPO), 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL), HMFS contained polyunsaturated fatty acids, and MLCT-type HMFS, as summarized in Table 1.

Fig. 1
figure 1

Enzymatic acidolysis for the synthesis of HMFS

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Table 1 HMFS synthesis through one-step acidolysis
Full size table

OPO and OPL are the 2 most abundant triacylglycerols in HMF [2, 5]. Numerous studies have been done on the synthesis of OPO but few studies related to OPL preparation, despite of the fact that it has been found that the content of OPL is even higher than that of OPO in some special regions, such as China [3, 13, 14]. Wang et al. [15] explored the possibility to prepare structured lipids rich in OPO and OPL by lipase-catalyzed acidolysis of fractionated palm stearin with oleic acid and linoleic acid.

Apart from OPO and OPL, polyunsaturated fatty acids, such as α-linolenic acid (ALA, C18:3), arachidonic acid (AA/ARA, C20:4), eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6), also play a crucial role for the structural, functional, neurological, and cognitive development of children [16, 17]. Herein, HMFS enriched with polyunsaturated fatty acids is of great interest as infant formulas. Fish oils [13], microbial oils [18], fungal oils [19] and plant oils [16] are the common sources for polyunsaturated fatty acids supplement. However, unsaturated fatty acids especially polyunsaturated fatty acids are prone to oxidation at high temperature, thus the reaction temperature and the stability of the products need to be taken into account [20]. Abed et al. [21] synthesized 1,3-dioleoyl-2-arachidonoylglycerol-rich structured lipids from microbial oil and oleic acid via Lipozyme RM IM-catalyzed acidolysis. Faustinl et al. [16] prepared HMFS rich in polyunsaturated fatty acids by acidolysis between tripalmitin and free fatty acids from camelina oil.

Medium chain fatty acids are also essential for infants, which help to induce the residual glyceride lipolysis and thus improve fat absorption [10, 22,23,24]. MLCT-type HMFS has become an attractive product, since it combines the benefits of medium chain fatty acids and long chain fatty acids. Peng et al. [9] synthesized OMO (1,3-oleic-2-medium chain)-type HMFS through Lipozyme RM IM-catalyzed acidolysis between Cinnamomum camphora seed oil and oleic acid. Zou et al. [25] produced MLCTs with high levels of lauric acid (C12:0) and DHA via an acidolysis reaction between algal oil and lauric acid.

In addition to one-step acidolysis, one-step transesterification is an alternative for HMFS synthesis with the typical reaction shown in Fig. 2. This process is normally performed between triacylglycerols and fatty acid esters or between different triacylglycerols. OPO, MLCT-type HMFS and other HMFS similar to HMF have been prepared successfully through this one-step transesterification process and the related research is summarized in Table 2.

Fig. 2
figure 2

Enzymatic transesterification for the synthesis of HMFS

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Table 2 HMFS synthesis through one-step transesterification
Full size table

During the transesterification process of triacylglycerols with fatty acid esters for HMFS preparation, fatty acid ethyl esters (FAEEs) is usually adopted as the acyl donor. Chen et al. [

Data availability statement

Not applicable.

Abbreviations

HMFS:

Human milk fat substitutes

HMF:

Human milk fat

TAG:

Triacylglycerol

PA:

Palmitic acid

OA:

Oleic acid

LA:

Linoleic acid

LCFA:

Long-chain fatty acid

MCFA:

Medium-chain fatty acid

PUFA:

Long-chain polyunsaturated fatty acid

MLCT:

Medium- and long-chain triglyceride

PPP:

Tripalmitin

FFA:

Free fatty acids

OPO:

Oleoyl-2-palmitoyl-3-oleoylglycerol

OPL:

Oleoyl-2-palmitoyl-3-linoleoylglycerol

ALA:

α-Linolenic acid

AA/ARA:

Arachidonic acid

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

OMO:

1,3-Oleic-2-medium chain

MAG:

Monoglyceride

USU:

Unsaturated–saturated-unsaturated

SFA:

Saturated fatty acid

FAEE:

Fatty acid ethyl ester

MUFA:

Monounsaturated fatty acid

CRL:

Lipases from candida rugosa

BCL:

Lipase from burkholderia cepacian

PPL:

Lipase from porcine pancreas

DAG:

Diglycerid

NCM:

Non-catalyzed mechanism

LCM:

Lipase-catalyzed mechanism

THF:

Tetrahydrofuran

OOO:

Triolei

References

  1. Ferreira-Dias S, Tecelão C. Human milk fat substitutes: advances and constraints of enzyme-catalyzed production. Lipid Technol. 2014;26:183–6. https://doi.org/10.1002/lite.201400043.

    Article  CAS  Google Scholar 

  2. Zhao J, Liu Q, Liu Y, Qiao W, Yang K, Jiang T, et al. Quantitative profiling of glycerides, glycerophosphatides and sphingolipids in Chinese human milk with ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. Food Chem. 2021;346:128857. https://doi.org/10.1016/j.foodchem.2020.128857.

    Article  CAS  PubMed  Google Scholar 

  3. Gao L, Cheng XY, Yu XW, Wang XS, ** QZ, Wang XG. Lipase-mediated production of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol by a two-step method. Food Biosci. 2020;36:100678. https://doi.org/10.1016/j.fbio.2020.100678.

    Article  CAS  Google Scholar 

  4. Abdi Hasibuan HA, Sitanggang AB, Andarwulan N, Hariyadi P. Enzymatic synthesis of human milk fat substitute—a review on technological approaches. Food Technol Biotechnol. 2021;59:475–95. https://doi.org/10.17113/ftb.59.04.21.7205.

    Article  CAS  Google Scholar 

  5. Şahin-Yeşilçubuk N, Akoh CC. Biotechnological and novel approaches for designing structured lipids intended for infant nutrition. J Am Oil Chem Soc. 2017;94:1005–34. https://doi.org/10.1007/s11746-017-3013-z.

    Article  CAS  Google Scholar 

  6. Jadhav HB, Annapure U. Designer lipids -synthesis and application—a review. Trends Food Sci Technol. 2021;116:884–902. https://doi.org/10.1016/j.tifs.2021.08.020.

    Article  CAS  Google Scholar 

  7. Xu WD. Enzymatic preparation of human milk fat substitutes rich in medium and long chain triacylglycerols. Wuxi: Jiangnan University; 2019.

    Google Scholar 

  8. Gil A, Ramirez M, Gil M. Role of long-chain polyunsaturated fatty acids in infant nutrition. Eur J Clin Nutr. 2003;57:S31–4. https://doi.org/10.1038/sj.ejcn.1601810.

    Article  CAS  PubMed  Google Scholar 

  9. Peng B, Yang J-Y, Liu X, Hu J-N, Zheng L-F, Li J, Deng Z-Y. Enzymatic synthesis of 1,3-oleic-2-medium chain triacylglycerols and strategy of controlling acyl migration: Insights from experiment and molecular dynamics simulation. Int J Food Prop. 2020;23:1082–96. https://doi.org/10.1080/10942912.2020.1775645.

    Article  CAS  Google Scholar 

  10. Korma SA, Zou X, Ali AH, Abed SM, ** Q, Wang X. Preparation of structured lipids enriched with medium- and long-chain triacylglycerols by enzymatic interesterification for infant formula. Food Bioprod Process. 2018;107:121–30. https://doi.org/10.1016/j.fbp.2017.11.006.

    Article  CAS  Google Scholar 

  11. Ghide MK, Yan Y. 1,3-Dioleoyl-2-palmitoyl glycerol (OPO)—enzymatic synthesis and use as an important supplement in infant formulas. J Food Biochem. 2021;45:225. https://doi.org/10.1111/jfbc.13799.

    Article  CAS  Google Scholar 

  12. Bryś J, Górska A, Ostrowska-Ligęza E, Wirkowska-Wojdyła M, Bryś A, Brzezińska R, et al. Human milk fat substitutes from lard and hemp seed oil mixtures. Appl Sci. 2021;11:7014. https://doi.org/10.3390/app11157014.

    Article  CAS  Google Scholar 

  13. Wei W, ** Q, Wang X. Human milk fat substitutes: past achievements and current trends. Prog Lipid Res. 2019;74:69–86. https://doi.org/10.1016/j.plipres.2019.02.001.

    Article  CAS  PubMed  Google Scholar 

  14. Wu W, Balter A, Vodsky V, Odetallh Y, Ben-Dror G, Zhang Y, Zhao A. Chinese breast milk fat composition and its associated dietary factors: a pilot study on lactating mothers in bei**g. Front Nutr. 2021;8:629. https://doi.org/10.3389/fnut.2021.606950.

    Article  CAS  Google Scholar 

  15. Wang XS, Jiang C, Di Xu W, Miu ZC, ** QZ, Wang XG. Enzymatic synthesis of structured triacylglycerols rich in 1,3-dioleoyl-2-palmitoylglycerol and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol in a solvent-free system. LWT. 2020;118: 108798. https://doi.org/10.1016/j.lwt.2019.108798.

    Article  CAS  Google Scholar 

  16. Faustino AR, Osório NM, Tecelão C, Canet A, Valero F, Ferreira-Dias S. Camelina oil as a source of polyunsaturated fatty acids for the production of human milk fat substitutes catalyzed by a heterologous rhizopus oryzae lipase. Eur J Lipid Sci Technol. 2016;118:532–44. https://doi.org/10.1002/ejlt.201500003.

    Article  CAS  Google Scholar 

  17. Jiang X, Zou X, Chao Z, Xu X. Preparation of human milk fat substitutes: a review. Life. 2022;12:187. https://doi.org/10.3390/life12020187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. He Y, Qiu C, Guo Z, Huang J, Wang M, Chen B. Production of new human milk fat substitutes by enzymatic acidolysis of microalgae oils from nannochloropsis oculata and isochrysis galbana. Bioresour Technol. 2017;238:129–38. https://doi.org/10.1016/j.biortech.2017.04.041.

    Article  CAS  PubMed  Google Scholar 

  19. Kim BH, Akoh CC. Recent research trends on the enzymatic synthesis of structured lipids. J Food Sci. 2015;80:C1713–24. https://doi.org/10.1111/1750-3841.12953.

    Article  CAS  PubMed  Google Scholar 

  20. Wang J, Wang X-D, Zhao X-Y, Liu X, Dong T, Wu F-A. From microalgae oil to produce novel structured triacylglycerols enriched with unsaturated fatty acids. Bioresour Technol. 2015;184:405–14. https://doi.org/10.1016/j.biortech.2014.09.133.

    Article  CAS  PubMed  Google Scholar 

  21. Abed SM, Zou X, Ali AH, ** Q, Wang X. Synthesis of 1,3-dioleoyl-2-arachidonoylglycerol-rich structured lipids by lipase-catalyzed acidolysis of microbial oil from mortierella alpina. Bioresour Technol. 2017;243:448–56. https://doi.org/10.1016/j.biortech.2017.06.090.

    Article  CAS  PubMed  Google Scholar 

  22. Xu W-D, Miao Z-C, Wang X-S, ** Q-Z, Wang X-G. Enzymatic synthesis of medium and long chain triacylglycerols. China Oils Fats. 2019;44:51–6.

    Google Scholar 

  23. Yuan T, Wei W, Wang X, ** Q. Biosynthesis of structured lipids enriched with medium and long-chain triacylglycerols for human milk fat substitute. LWT. 2020;128:109255. https://doi.org/10.1016/j.lwt.2020.109255.

    Article  CAS  Google Scholar 

  24. Li Y, Li C, Feng F, Wei W, Zhang H. Synthesis of medium and long-chain triacylglycerols by enzymatic acidolysis of algal oil and lauric acid. LWT. 2021;136:110309. https://doi.org/10.1016/j.lwt.2020.110309.

    Article  CAS  Google Scholar 

  25. Zou X, Ye L, He X, Wu S, Zhang H, ** Q. Preparation of DHA-rich medium- and long-chain triacylglycerols by lipase-catalyzed acidolysis of microbial oil from schizochytrium sp.with medium-chain fatty acids. Appl Biochem Biotechnol. 2020;191:1294–314. https://doi.org/10.1007/s12010-020-03261-6.

    Article  CAS  PubMed  Google Scholar 

  26. **ao QH, Xu YQ, **ong H, Hu JN, Zhu XM, Zhang YY. Effect of solvent and water activity on acyl migration in thesynthesis of OPO structural lipids. China Oils Fats. 2020;45:62–7.

    Google Scholar 

  27. Gao L, Xu X-W, Zou F, Cheng XY, Yang ZZ, Wang XS, et al. Enzymatic synthesis of structured lipids rich in 1-oleoyl-2-palmitoyl-3-linoleylglycerol. China Oils Fats. 2020;45:66–70.

    CAS  Google Scholar 

  28. Wang J, Liu X, Wang X-D, Dong T, Zhao X-Y, Zhu D, et al. Selective synthesis of human milk fat-style structured triglycerides from microalgal oil in a microfluidic reactor packed with immobilized lipase. Bioresour Technol. 2016;220:132–41. https://doi.org/10.1016/j.biortech.2016.08.023.

    Article  CAS  PubMed  Google Scholar 

  29. Zou X-G, Hu J-N, Zhao M-L, Zhu X-M, Li H-Y, Liu X-R, et al. Lipozyme RM IM-catalyzed acidolysis of cinnamomum camphora seed oil with oleic acid to produce human milk fat substitutes enriched in medium-chain fatty acids. J Agric Food Chem. 2014;62:10594–603. https://doi.org/10.1021/jf503691p.

    Article  CAS  PubMed  Google Scholar 

  30. Chen F, Yu-Lan Ye, **ong H, Hu J-N, Zhu X-M. Preparation of butter-based breast milk fat substitute by enzymatic catalysis. J Chin Inst Food Sci Technol. 2020;20:74–85.

    Google Scholar 

  31. Chen B, Zhang H, Cheong L-Z, Tan T, Xu X. Enzymatic production of ABA-type structured lipids containing omega-3 and medium-chain fatty acids: effects of different acyl donors on the acyl migration rate. Food Bioprocess Technol. 2012;5:541–7. https://doi.org/10.1007/s11947-009-0322-8.

    Article  CAS  Google Scholar 

  32. Srivastava A, Akoh CC, Chang S-W, Lee G-C, Shaw J-F. Candida rugosa lipase LIP1-catalyzed transesterification to produce human milk fat substitute. J Agric Food Chem. 2006;54:5175–81. https://doi.org/10.1021/jf060623h.

    Article  CAS  PubMed  Google Scholar 

  33. Zou X, ** Q, Guo Z, Xu X, Wang X. Preparation and characterization of human milk fat substitutes based on triacylglycerol profiles. J Am Oil Chem Soc. 2016;93:781–92. https://doi.org/10.1007/s11746-016-2816-7.

    Article  CAS  Google Scholar 

  34. Zhang C-Y, **n J-Y, Chen L-L, Wang Y. Advances in enzymatic preparation of human milk fat substitutes. Food Sci. 2013;34:298–302.

    Google Scholar 

  35. Wei W, Sun C, Wang X, ** Q, Xu X, Akoh CC, Wang X. Lipase-catalyzed synthesis of Sn-2 palmitate: a review. Engineering. 2020;6:406–14. https://doi.org/10.1016/j.eng.2020.02.008.

    Article  CAS  Google Scholar 

  36. Wu Y-Q, Wang X-H, Wang X-S, ** Q-Z, Wang X-G. Advance in acyl migration in the reaction of enzymatic acidolysis to synthesize structured lipids. China Oils Fats. 2021;2:20–7.

    Google Scholar 

  37. Soumanou MM, Pérignon M, Villeneuve P. Lipase-catalyzed interesterification reactions for human milk fat substitutes production: a review. Eur J Lipid Sci Technol. 2013;115:270–85. https://doi.org/10.1002/ejlt.201200084.

    Article  CAS  Google Scholar 

  38. Tecelão C, Perrier V, Dubreucq E, Ferreira-Dias S. Production of human milk fat substitutes by interesterification of tripalmitin with ethyl oleate catalyzed by candida parapsilosis lipase/acyltransferase. J Am Oil Chem Soc. 2019;96:777–87. https://doi.org/10.1002/aocs.12250.

    Article  CAS  Google Scholar 

  39. Qiu H, Ma L, Liang C, Zhang H, Liu G-Q. Effect of palm stearin oil (PSO), physical fractionation oil of palm stearin oil (PPP) and structured lipids of rich 1,3-dioleoyl-2-palmitoylglycerol (OPO) on the stability in different emulsion systems. J Oleo Sci. 2019;68:607–14. https://doi.org/10.5650/jos.ess19021.

    Article  CAS  PubMed  Google Scholar 

  40. Zong L, Bi Y-L, Cheng Y-P. Synthesis of OPO by enzymatic transesterification of ethyl oleate with palm stearin. China Oils Fats. 2020;45:82–7.

    Google Scholar 

  41. Zou X, Huang J, ** Q, Guo Z, Cheong L, Xu X, Wang X. Preparation of human milk fat substitutes from lard by lipase-catalyzed interesterification based on triacylglycerol profiles. J Am Oil Chem Soc. 2014;34:1243. https://doi.org/10.1007/s11746-014-2533-z.

    Article  CAS  Google Scholar 

  42. Zhong J-F, Qin X-L, Wang Y-H. Research progress in enzymatic production and evaluation of human milk fat substitutes. Sci Technol Food Ind. 2014;35:377–84.

    CAS  Google Scholar 

  43. Turan D, SahinYeşilçubuk N, Akoh CC. Production of human milk fat analogue containing docosahexaenoic and arachidonic acids. J Agric Food Chem. 2012;60:4402–7. https://doi.org/10.1021/jf3012272.

    Article  CAS  PubMed  Google Scholar 

  44. Robles A, Jiménez MJ, Esteban L, González PA, Martín L, Rodríguez A, Molina E. Enzymatic production of human milk fat substitutes containing palmitic and docosahexaenoic acids at sn-2 position and oleic acid at sn-1,3 positions. LWT Food Sci Technol. 2011;44:1986–92. https://doi.org/10.1016/j.lwt.2011.05.022.

    Article  CAS  Google Scholar 

  45. Kotani K, Yamamoto Y, Hara S. Enzymatic preparation of human milk fat substitutes and their oxidation stability. J Oleo Sci. 2015;64:275–81. https://doi.org/10.5650/jos.ess14254.

    Article  CAS  PubMed  Google Scholar 

  46. Liu C, Tian J, Zhang R, Xu J, Nie K, Deng L, Wang F. Solvent-free alcoholysis of tripalmitin to produce 2-Monoglyceride as precursor for 1, 3-oleoyl-2-palmitoylglycerol. Appl Biochem Biotechnol. 2020;190:867–79. https://doi.org/10.1007/s12010-019-03136-5.

    Article  CAS  PubMed  Google Scholar 

  47. Agapay RC, Ju Y-H, Tran-Nguyen PL, Ismadji S, Angkawijaya AE, Go AW. Process evaluation of solvent-free lipase-catalyzed esterification schemes in the synthesis of structured triglycerides from oleic and palmitic acids. Asia-Pac J Chem Eng. 2021;16:190. https://doi.org/10.1002/apj.2606.

    Article  CAS  Google Scholar 

  48. Wei W, Feng Y, Zhang X, Cao X, Feng F. Synthesis of structured lipid 1,3-dioleoyl-2-palmitoylglycerol in both solvent and solvent-free system. LWT Food Sci Technol. 2015;60:1187–94. https://doi.org/10.1016/j.lwt.2014.09.013.

    Article  CAS  Google Scholar 

  49. **ong Z-Q, Pan L-J, Jiang S-T, Shen H, Cao L-L. Optimization of two-step lipase-catalyzed synthesis of human milk fat substitutes by response surface methodology and fatty acid composition analysis. Food Sci. 2017;38:248–54.

    Google Scholar 

  50. Ogasawara S, Ogawa S, Yamamoto Y, Hara S. Enzymatic preparation and oxidative stability of human milk fat substitute containing polyunsaturated fatty acid located at sn-2 position. J Oleo Sci. 2020;69:825–35. https://doi.org/10.5650/jos.ess19332.

    Article  CAS  PubMed  Google Scholar 

  51. Wang X, Zou W, Sun X, Zhang Y, Wei L, ** Q, Wang X. Chemoenzymatic synthesis of 1,3-dioleoyl-2-palmitoylglycerol. Biotechnol Lett. 2015;37:691–6. https://doi.org/10.1007/s10529-014-1714-z.

    Article  CAS  PubMed  Google Scholar 

  52. Sarmah N, Revathi D, Sheelu G, Yamuna Rani K, Sridhar S, Mehtab V, Sumana C. Recent advances on sources and industrial applications of lipases. Biotechnol Progress. 2018;34:5–28. https://doi.org/10.1002/btpr.2581.

    Article  CAS  Google Scholar 

  53. Kazlauskas RJ. Elucidating structure-mechanism relationships in lipases: prospects for predicting and engineering catalytic properties. Trends Biotechnol. 1994;12:464–72. https://doi.org/10.1016/0167-7799(94)90022-1.

    Article  CAS  PubMed  Google Scholar 

  54. Liu S-L, Liu W, Dong X-Y, Wei F, Lv X, Zhong J, Chen H. Research progress on positional selectivity of enzymatic synthesis of structured lipid. J Agric Sci Technol. 2014;16:59–67.

    CAS  Google Scholar 

  55. Cao X, Wang D, Yuan Y-J. 2020 Advances in lipase regioselectivity and its applications in synthesis of functional structured triacylglycerols. 46: 295–301

  56. Pina-Rodriguez AM, Akoh CC. Synthesis and characterization of a structured lipid from amaranth oil as a partial fat substitute in milk-based infant formula. J Agric Food Chem. 2009;57:6748–56. https://doi.org/10.1021/jf901048x.

    Article  CAS  PubMed  Google Scholar 

  57. Wang Z, Liu L, Liu L, Liu T, Li C, Sun L. 1,3-Dioleoyl-2-palmitoylglycerol-rich triacylglycerol characterization by three processing methods. Int J Food Prop. 2019;22:1156–71. https://doi.org/10.1080/10942912.2019.1632345.

    Article  CAS  Google Scholar 

  58. Karabulut I, Durmaz G, Hayaloglu AA. C18 Unsaturated fatty acid selectivity of lipases during the acidolysis reaction between tripalmitin and oleic, linoleic, and linolenic acids. J Am Oil Chem Soc. 2010;87:1301–7. https://doi.org/10.1007/s11746-010-1613-y.

    Article  CAS  Google Scholar 

  59. Song X, Qi X, Hao B, Qu Y. Studies of substrate specificities of lipases from different sources. Eur J Lipid Sci Technol. 2008;110:1095–101. https://doi.org/10.1002/ejlt.200800073.

    Article  CAS  Google Scholar 

  60. Lee C-H. Effect of water activity and immobilization on fatty acid selectivity for esterification reactions mediated by lipases. Biotechnol Bioeng. 2001;75:219–27.

    Article  CAS  PubMed  Google Scholar 

  61. Kovalenko GA, Perminova LV, Beklemishev AB, Mamaev AL, Patrushev YV. Biocatalytic heterogeneous processes of the esterification of saturated fatty acids with aliphatic alcohols. Catal Ind. 2018;10:68–74. https://doi.org/10.1134/S2070050418010075.

    Article  Google Scholar 

  62. Wu P, Li Q, Zhang Y-J, Wang Z, Zheng J-Y. Investigation on the acyl chain length specificity of lipase by gas chromatography assay. Chem Pap. 2020;74:3039–45. https://doi.org/10.1007/s11696-020-01143-z.

    Article  CAS  Google Scholar 

  63. Duan X, **ang M, Wang L, Yan Q, Yang S, Jiang Z. Biochemical characterization of a novel lipase from malbranchea cinnamomea suitable for production of lipolyzed milkfat flavor and biodegradation of phthalate esters. Food Chem. 2019;297: 124925. https://doi.org/10.1016/j.foodchem.2019.05.199.

    Article  CAS  PubMed  Google Scholar 

  64. Misbah A, Koraichi SI, Jouti MAT. Purification, characterization and immobilization of lipase from proteus vulgaris OR34 for synthesis of methyl oleate. Microbiol Biotechnol Lett. 2020;48:491–505. https://doi.org/10.48022/mbl.2003.03010.

    Article  CAS  Google Scholar 

  65. Rivero-Pino F, Padial-Dominguez M, Guadix EM, Morales-Medina R. Novozyme 435 and lipozyme RM IM preferably esterify polyunsaturated fatty acids at the sn-2 position. Eur J Lipid Sci Technol. 2020;122:2000115. https://doi.org/10.1002/ejlt.202000115.

    Article  CAS  Google Scholar 

  66. Utsugi A, Kanda A, Hara S. Lipase specificity in the transacylation of triacylglycerin. J Oleo Sci. 2009;58:123–32. https://doi.org/10.5650/jos.58.123.

    Article  CAS  PubMed  Google Scholar 

  67. Karabulut I, Durmaz G, Hayaloglu AA. Fatty acid selectivity of lipases during acidolysis reaction between triolein and saturated fatty acids varying from caproic to behenic acids. J Agric Food Chem. 2009;57:7584–90. https://doi.org/10.1021/jf901755h.

    Article  CAS  PubMed  Google Scholar 

  68. Karabulut I, Durmaz G, Hayaloglu AA. Fatty acid selectivity of lipases during acidolysis reaction between oleic acid and monoacid triacylglycerols. J Agric Food Chem. 2009;57:10466–70. https://doi.org/10.1021/jf902816e.

    Article  CAS  PubMed  Google Scholar 

  69. Gonçalves MCP, Amaral JC, Lopes LA, Fernandez-Lafuente R, Tardioli PW. Stabilization and operational selectivity alteration of Lipozyme 435 by its coating with polyethyleneimine: comparison of the biocatalyst performance in the synthesis of xylose fatty esters. Int J Biol Macromol. 2021;192:665–74. https://doi.org/10.1016/j.ijbiomac.2021.10.052.

    Article  CAS  PubMed  Google Scholar 

  70. Nurullina PV, Perminova LV, Kovalenko GA. Catalytic properties of rPichia/lip lipase adsorbed on carbon nanotubes in the low-temperature synthesis of esters. Moscow Univ Chem Bull. 2020;75:110–4. https://doi.org/10.3103/S0027131420020108.

    Article  Google Scholar 

  71. Jo E, Kim J, Lee A, Moon K, Cha J. Identification and characterization of a novel thermostable GDSL-type lipase from geobacillus thermocatenulatus. J Microbiol Biotechnol. 2021;31:483–91. https://doi.org/10.4014/jmb.2012.12036.

    Article  CAS  PubMed  Google Scholar 

  72. Chen Y, Cheong L-Z, Zhao J, Panpipat W, Wang Z, Li Y, et al. Lipase-catalyzed selective enrichment of omega-3 polyunsaturated fatty acids in acylglycerols of cod liver and linseed oils: modeling the binding affinity of lipases and fatty acids. Int J Biol Macromol. 2019;123:261–8. https://doi.org/10.1016/j.ijbiomac.2018.11.049.

    Article  CAS  PubMed  Google Scholar 

  73. Lima RT, Alves AM, de Paula AV, de Castro HF, Andrade GSS. Mycelium-bound lipase from Penicillium citrinum as biocatalyst for the hydrolysis of vegetable oils. Biocatal Agric Biotechnol. 2019;22: 101410. https://doi.org/10.1016/j.bcab.2019.101410.

    Article  Google Scholar 

  74. Machado SA, Da Rós PCM, de Castro HF, Giordani DS. Hydrolysis of vegetable and microbial oils catalyzed by a solid preparation of castor bean lipase. Biocatal Agric Biotechnol. 2021;37: 102188. https://doi.org/10.1016/j.bcab.2021.102188.

    Article  CAS  Google Scholar 

  75. Gao K, Chu W, Sun J, Mao X. Identification of an alkaline lipase capable of better enrichment of EPA than DHA due to fatty acids selectivity and regioselectivity. Food Chem. 2020;330: 127225. https://doi.org/10.1016/j.foodchem.2020.127225.

    Article  CAS  PubMed  Google Scholar 

  76. Castejón N, Señoráns FJ. Strategies for enzymatic synthesis of omega-3 structured triacylglycerols from camelina sativa oil enriched in EPA and DHA. Eur J Lipid Sci Technol. 2019;121:1800412.

    Article  Google Scholar 

  77. Akanbi TO, Barrow CJ. Candida antarctica lipase A effectively concentrates DHA from fish and thraustochytrid oils. Food Chem. 2017;229:509–16. https://doi.org/10.1016/j.foodchem.2017.02.099.

    Article  CAS  PubMed  Google Scholar 

  78. Corzo-Martínez M, López E, Vázquez L, Ortego E, Olaya E, Reglero G, Torres CF. Lipase-catalyzed butanolysis of echium oil for the selective enrichment in gamma-linolenic and stearidonic acids. Eur J Lipid Sci Technol. 2018;120:1800251. https://doi.org/10.1002/ejlt.201800251.

    Article  CAS  Google Scholar 

  79. Barbosa MS, Freire CCC, Almeida LC, Freitas LS, Souza RL, Pereira EB, et al. Optimization of the enzymatic hydrolysis of Moringa oleifera Lam oil using molecular docking analysis for fatty acid specificity. Biotechnol Appl Biochem. 2019;66:823–32. https://doi.org/10.1002/bab.1793.

    Article  CAS  PubMed  Google Scholar 

  80. Qin X, Zhong J, Wang Y. A mutant T1 lipase homology modeling, and its molecular docking and molecular dynamics simulation with fatty acids. J Biotechnol. 2021;337:24–34. https://doi.org/10.1016/j.jbiotec.2021.06.024.

    Article  CAS  PubMed  Google Scholar 

  81. Cai Y, **ng S, Zhang Q, Zhu R, Cheng K, Li C, et al. Expression, purification, properties, and substrate specificity analysis of Aspergillus niger GZUF36 lipase in Escherichia coli. Process Biochem. 2021;111:118–27. https://doi.org/10.1016/j.procbio.2021.09.002.

    Article  CAS  Google Scholar 

  82. de Rodrigues CA, Barbosa MS, dos Santos JCB, Lisboa MC, Souza RL, Pereira MM, et al. Computational and experimental analysis on the preferential selectivity of lipases for triglycerides in licuri oil. Bioprocess Biosyst Eng. 2021;44:2141–51. https://doi.org/10.1007/s00449-021-02590-y.

    Article  CAS  Google Scholar 

  83. Oh J-E, Lee K-W, Park H-K, Kim J-Y, Kwon K-I, Kim J-W, et al. Lipase-catalyzed acidolysis of olive oil with capric acid: effect of water activity on incorporation and acyl migration. J Agric Food Chem. 2009;57:9280–3. https://doi.org/10.1021/jf9023245.

    Article  CAS  PubMed  Google Scholar 

  84. Mao J, Hu Z, Hu J, Zhu X, **ong H. A density functional theory (DFT) study of the acyl migration occurring during lipase-catalyzed transesterifications. IJMS. 2019;20:3438. https://doi.org/10.3390/ijms20143438.

    Article  CAS  PubMed Central  Google Scholar 

  85. Ji Y-Z, Cheng Y-L, Ren L-N, Yang T-T, Zhao Y-X. Advances on 1,3-dioleoyl-2-palmitoyl glycerol as human milk fat substitutes. Chem Life. 2017;37:789–96.

    Google Scholar 

  86. Zhang Z, Lee WJ, Wang Y. Evaluation of enzymatic interesterification in structured triacylglycerols preparation: a concise review and prospect. Crit Rev Food Sci Nutr. 2021;61:3145–59. https://doi.org/10.1080/10408398.2020.1793725.

    Article  CAS  PubMed  Google Scholar 

  87. Martinelle M, Hult K. Kinetics of acyl transfer reactions in organic media catalysed by Candida Antarctica lipase B kinetics of acyl transfer reactions in organic media catalysed by Candida Antarctica lipase B. Biochimica Biophys Acta. 1995;1251:191–7.

    Article  Google Scholar 

  88. Joseph B, Ramteke PW, Thomas G. Cold active microbial lipases: some hot issues and recent developments. Biotechnol Adv. 2008;26:457–70. https://doi.org/10.1016/j.biotechadv.2008.05.003.

    Article  CAS  PubMed  Google Scholar 

  89. Duan Z-Q, Du W, Liu D-H. The mechanism of solvent effect on the positional selectivity of candida antarctica lipase B during 1,3-diolein synthesis by esterification. Bioresour Technol. 2011;102:11048–50. https://doi.org/10.1016/j.biortech.2011.09.003.

    Article  CAS  PubMed  Google Scholar 

  90. Bi Y, Duan Z, Zhang W, Xu L, Wang Z, Zhao X, et al. Evaluation of the Candida sp. 99–125 lipase positional selectivity for 1,3-diolein synthesis. Biomed Res Int. 2019;2019:4318631. https://doi.org/10.1155/2019/4318631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. ZitianWang DL, Liu D, Liu H, Du W. Kinetics and mechanism of solvent influence on the lipase-catalyzed 1,3-diolein synthesis. ACS Omega. 2020;5:24708–16. https://doi.org/10.1021/acsomega.0c03284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Li C, Zhang F, Gao Z, He L, Zeng X, Zhu Q, Yu L. Effects of organic solvent, water activity, and salt hydrate pair on the sn-1,3 selectivity and activity of whole-cell lipase from Aspergillus niger GZUF36. Appl Microbiol Biotechnol. 2018;102:225–35. https://doi.org/10.1007/s00253-017-8597-6.

    Article  CAS  PubMed  Google Scholar 

  93. Wang X, Zhao X, Yang Z, Wang X, Wang T. Effect of solvent on acyl migration of 2-monoacylglycerols in enzymatic ethanolysis. J Agric Food Chem. 2020;68:12358–64. https://doi.org/10.1021/acs.jafc.0c05578.

    Article  CAS  PubMed  Google Scholar 

  94. Duan Z-Q, Du W, Liu D-H. The solvent influence on the positional selectivity of novozym 435 during 1,3-diolein synthesis by esterification. Bioresour Technol. 2010;101:2568–71. https://doi.org/10.1016/j.biortech.2009.11.087.

    Article  CAS  PubMed  Google Scholar 

  95. Wang Z-T, Su X-J, Du W, Dai L-M, Liu D-H. Lipozyme TL IM-catalyzed esterification of oleic acid for 1,3-diacylglycerol preparation. J Chinese Univers. 2015;36:1535–41.

    CAS  Google Scholar 

  96. Duan Z-Q, Du W, Liu D-H. The pronounced effect of water activity on the positional selectivity of novozym 435 during 1,3-diolein synthesis by esterification. Catal Commun. 2010;11:356–8. https://doi.org/10.1016/j.catcom.2009.10.030.

    Article  CAS  Google Scholar 

  97. Peng B, Chen F, Liu X, Hu J-N, Zheng L-F, Li J, Deng Z-Y. Trace water activity could improve the formation of 1,3-oleic-2-medium chain-rich triacylglycerols by promoting acyl migration in the lipase RM IM catalyzed interesterification. Food Chem. 2020;313: 126130. https://doi.org/10.1016/j.foodchem.2019.126130.

    Article  CAS  PubMed  Google Scholar 

  98. Li W, Du W, Li Q, Sun T, Liu D. Study on acyl migration kinetics of partial glycerides: dependence on temperature and water activity. J Mol Catal B Enzym. 2010;63:17–22. https://doi.org/10.1016/j.molcatb.2009.11.012.

    Article  CAS  Google Scholar 

  99. Chen Y, Meng Z, Liu Y-F. Acidolysis of palmitic acid and oil–tea camellia seed oil catalyzed by lipozyme RM IM in solvent-free system. China Oils Fats. 2013;38:23–6.

    CAS  Google Scholar 

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Acknowledgements

The authors express their gratitude to the support from Dongguan Science and Technology Bureau (Innovative R and D Team Leadership of Dongguan City, 201536000100033).

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Dongguan Science and amp; Technology Bureau (Innovative R and amp; D Team Leadership of Dongguan City), 201536000100033

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Authors and Affiliations

  1. Key Laboratory for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Bei**g, 100084, China

    Zeqing Liu, Lingmei Dai, Dehua Liu & Wei Du

  2. Tsinghua Innovation Center in Dongguan, Dongguan, 523808, Guangdong, China

    Dehua Liu

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ZQL: literature collection and manuscript writing; LMD: literature collection and analysis; DHL: content design; WD: content design, revision and project administration. All authors read and approved the final manuscript.

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Liu, Z., Dai, L., Liu, D. et al. Progress and perspectives of enzymatic preparation of human milk fat substitutes. Biotechnol Biofuels 15, 118 (2022). https://doi.org/10.1186/s13068-022-02217-8

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