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Aromas flow: eco-friendly, continuous, and scalable preparation of flavour esters


Flow-based biocatalysis offers advantages to perform multiphase reactions, including liquid–liquid reactions, due to intensified mass transfer, compartmentalization and high local concentration of the catalyst. Enzymatic immobilization leads to stable biocatalysts, with the possibility to incorporate them in continuous reactors. The combination between the two technologies allows for intensified process with high substrate concentration and high product recovery. The present paper is an excellent example of automated continuous biocatalytic process where a transferase from Mycobacterium smegmatis (MsAcT) was immobilized onto agarose beads and exploited for the preparation of a variety of flavour-esters, utilizing exclusively natural substrates, with excellent yields in 5-min reaction times. The corresponding products can be labelled and commercialized as natural too, thus increasing their market value.

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  1. Sheldon RA, Pereira PC (2017). Chem Soc Rev 46:2678–2691

    Article  CAS  Google Scholar 

  2. Berger RG (2009). Biotechnol Lett 31:1651–1659

    Article  CAS  Google Scholar 

  3. Hofmann T, Krautwurst D, Schieberle P (2018). J Agric Food Chem 66:2197–2203

    Article  CAS  Google Scholar 

  4. Dhake KP, Thakare DD, Bhanage BM (2013). Lipase: Flavour Fragrance J 28:71–83

    CAS  Google Scholar 

  5. Anobom D, Pinheiro AS, De Andrade RA, Aguieiras ECG, Andrade GC, Moura MV, Almeida RV, Freire DM (2014). Biomed Res Int 2014:Article ID 684506

    Article  Google Scholar 

  6. De Vitis V, Nakhnoukh C, Pinto A, Contente ML, Barbiroli A, Milani M, Bolognesi M, Molinari F, Gourlay LJ, Romano D (2017). FEBS J 285:903–914

    Article  Google Scholar 

  7. Halling PJ (1990). Biotechnol Bioeng 35:691–701

    Article  CAS  Google Scholar 

  8. Spizzo P, Basso A, Ebert C, Gardossi L, Ferrario V, Romano D, Molinari F (2007). Tetrahedron 63:11005–11010

    Article  CAS  Google Scholar 

  9. Tacias-Pascacio VG, Peirce S, Torrestiana-Sanchez B, Yates M, Rosales-Quintero A, Virgen-Ortiz JJ, Roberto Fernandez-Lafuente R (2016). RSC Adv 6:100281–100294

    Article  CAS  Google Scholar 

  10. Engel S, Höck H, Bocola M, Keul H, Schwaneberg U, Möller M (2016). Polymers 8:524

    Article  Google Scholar 

  11. Gandolfi R, Converti A, Pirozzi D, Molinari F (2001). J Biotechnol 92:21–26

    Article  CAS  Google Scholar 

  12. Converti A, Del Borghi A, Gandolfi R, Lodi A, Molinari F, Palazzi E (2002). Biotechnol Bioeng 77:232–237

    Article  CAS  Google Scholar 

  13. Converti, A.; Gandolfi, R.; Zilli, M.; Molinari, F.; Binaghi, L.; Perego P, Del Borghi M. Appl Microbiol Biotechnol 2005, 67:637–640

    Article  CAS  Google Scholar 

  14. Mathews I, Soltis M, Saldajeno M, Ganshaw G, Sala R, Weyler W, Cervin MA, Whited G, Bott R (2007). Biochemistry 46:8969–8979

    Article  CAS  Google Scholar 

  15. Kazemi M, Sheng X, Kroutil W, Himo F (2018). ACS Catal 8:10698–10706

    Article  CAS  Google Scholar 

  16. Wiermans L, Hofzumahaus S, Schotten C, Weigand L, Schallmey M, Schallmey A, Domıńguez de Marıá P (2013). ChemCatChem 5:3719–3724

    Article  CAS  Google Scholar 

  17. de Leeuw N, Torrelo G, Bisterfeld C, Resch V, Mestrom L, Straulino E, van der Weel L, Hanefeld U (2018). Adv Synth Catal 360:242–249

    Article  Google Scholar 

  18. Perdomo Chiarelli I, Gianolio S, Pinto A, Romano D, Contente ML, Paradisi F, Molinari F (2019). J Agric Food Chem 67:6517–6522

    Article  Google Scholar 

  19. Mestrom L, Claessen JGR, Hanefeld U (2019). ChemCatChem 11:2004–2010

    Article  CAS  Google Scholar 

  20. Land H, Hendil-Forssell P, Martinelle M, Berglund P (2016). Catal Sci Technol 6:2897–2900

    Article  CAS  Google Scholar 

  21. Contente ML, Pinto A, Molinari F, Paradisi F (2018). Adv Synth Catal 360:4814–4819

    Article  CAS  Google Scholar 

  22. Contente ML, Farris S, Tamborini L, Molinari F, Paradisi F (2019). Green Chem 21:3263–3266

    Article  CAS  Google Scholar 

  23. Wohlgemuth R, Plazl I, Znidarsic-Plazl P, Gernaey KV, Woodley JM (2015). Trends Biotechnol 33:302–314

    Article  CAS  Google Scholar 

  24. Tamborini L, Fernandes P, Paradisi F, Molinari F (2018). Trends Biotechnol 36:73–88

    Article  CAS  Google Scholar 

  25. Junior II, Flores MC, Sutili FK, Leite SGF, de Miranda LSM, Leal ICR, de Souza ROMA (2012). Org Process Res Dev 16:1098–1101

    Article  CAS  Google Scholar 

  26. Tamborini L, Romano D, Pinto A, Contente M, Iannuzzi MC, Conti P, Molinari F (2013). Tetrahedron Lett 54:6090–6093

    Article  CAS  Google Scholar 

  27. Wang SS, Li ZJ, Sheng S, Wu FA, Wang J (2016). J Chem Technol Biotechnol 91:555–562

    Article  CAS  Google Scholar 

  28. Zambelli P, Tamborini L, Cazzamalli S, Pinto A, Arioli S, Balzaretti S, Plou FJ, Fernandez-Arrojo L, Molinari F, Conti P, Romano D (2016). Food Chem 190:607–613

    Article  CAS  Google Scholar 

  29. Novak U, Lavric D, Žnidaršič-Plazl P (2016). J Flow Chem 6:33–38

    Article  CAS  Google Scholar 

  30. Contente ML, Dall’Oglio F, Tamborini L, Molinari F, Paradisi F (2017). ChemCatChem 9:3843–3848

    Article  CAS  Google Scholar 

  31. Weeranoppanant N (2019). React Chem Eng 4:235–243

    Article  CAS  Google Scholar 

  32. Tanimu A, Jaenicke S, Alhooshani K (2017). Chem Eng J 327:792–821

    Article  CAS  Google Scholar 

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This project was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N. 792804 AROMAs-FLOW (M.L.C.).

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In this manuscript, the work of Dr. Martina Contente (Marie Curie Fellow) has been capture in its essence with the design of a highly sustainable strategy for the preparation of natural flavour esters, using exclusively reagents found in nature. The precious collaboration with Prof. Molinari and Prof. Tamborini (co-corresponding author) has been key for the optimisation of flow set-up. Thirty different fragrances have been synthesised with an extremely versatile acyl transferase from M. smegmatis. The immobilised biocatalyst (just 1.9 mg) enabled extremely rapid reaction times (residence time was optimised to 5 minutes) in a biphasic system, without any loss of activity after a week of continuous operation.

Corresponding authors

Correspondence to Lucia Tamborini or Francesca Paradisi.

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Article Highlights

1. Flavour-ester formation was performed in an aqueous medium using an immobilized transferase from Mycobacterium smegmatis (MsAcT).

2. Flow-based strategy leads to intensified processes with high substrate loading, yields and unprecedented reaction times.

3. Natural substrates processed via enzymatic reaction allow for the commercialization of the corresponding products as natural too.

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Contente, M.L., Tamborini, L., Molinari, F. et al. Aromas flow: eco-friendly, continuous, and scalable preparation of flavour esters. J Flow Chem 10, 235–240 (2020).

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  • Flow biocatalysis
  • Multiphase reaction
  • MsAcT
  • Flavour-esters
  • Intensified processes