CHEM21 Case Study: Biocatalysis in Bio-derived Solvents

One of the major obstacles to industrial uptake of biocatalysis is the difficulty in achieving similar reaction conditions to those of organic chemical reactions.[1] In biotransformations, water is traditionally used as the reaction solvent. However, there are many associated issues with the use of water as the reaction medium. These include issues with the solubility of the organic substrates (which generally require the addition of an organic water-soluble co-solvent), purification and enzyme recovery, as well as the incurred cost and environmental impact of contaminated aqueous waste treatment.[2] 

These issues can be overcome by the use of organic solvents as the reaction media, an approach that is well established in academic research but is not common in industrial applications.[3][4] However, the approach to the use of organic solvents in enzymatic reactions has been somewhat incidental. There have been limited studies into the use of “green” solvents as reaction media for enzymatic transformations and include the use of ionic liquids, supercritical CO2 and some bio-derived solvent.[5][6] The CHEM21 researchers investigated a more systematic approach in assessing the behaviour of supported Candida Antarctica lipase B (Novozyme 435) in 24 organic solvents including classical as well as bio-derived solvents (Figure 1); this was investigated through carrying out a kinetic study of the reaction of hexanol with dodecanoic acid to produce the industrially relevant hexyl laurate, used in the personal care and cosmetics industries.[2]  

The researchers observed a correlation between high activity of Novozyme 435 and solvent properties, specifically hydrogen-bond accepting ability and molar volume. In comparison to previous studies, the study found that molar concentration was an important factor; it is hypothesised that this is related to the partition coefficient (log P) and its ability to remove structural water from the enzyme active site.  The bioderived solvents that performed best were limonene and p-cymene with the former outperforming the classically used hexane, offering an effective and sustainable approach for industrial fatty acid ester synthesis.[2]

Figure 1: Kinetic Screening for Novozyme 435 mediated esterification reaction of hexanol with dodecanoic acid, in a variety of organic solvents (Reproduced from G. Paggiola et al [2] with permission of The Royal Society of Chemistry)

Figure 1: Kinetic Screening for Novozyme 435 mediated esterification reaction of hexanol with dodecanoic acid, in a variety of organic solvents (Reproduced from G. Paggiola et al [2] with permission of The Royal Society of Chemistry)

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  1. S. Wenda, S. Illner, A. Mell and U. Kragl, Industrial biotechnology-the future of green chemistry?, Green Chem., 2011, 13, 3007-3047.
  2. G. Paggiola, A. J. Hunt, J. McElroy Con R and Sherwood and J. H. Clark, Biocatalysis in bio-derived solvents: an improved approach for medium optimisation, Green Chem., 2014, 16, 2107–2110.
  3. Enzyme Catalysis in Organic Synthesis, (ed. H. Gröger and O. May) Wiley-VCH Verlag GmbH & Co. KGaA, 2012.
  4. C. Jimenez-Gonzalez, P. Poechlauer, Q. B. Broxterman, B. – S. Yang, Dam Ende, J. Baird, C. Bertsch, R. E. Hannah, P. Dell’Orco, H. Noorman, S. Yee, R. Reintjens, A. Wells, V. Massonneau and J. Manley, Key Green Engineering Research Areas for Sustainable Manufacturing: A Perspective from Pharmaceutical and Fine Chemicals Manufacturers, Org. Process Res. Dev., 2011, 15, 900-911.
  5. M. J. Hernáiz, A. R. Alcántara, J. I. García and J. V. Sinisterra, Applied Biotransformations in Green Solvents, Chem. Eur. J., 2010, 16, 9422-9437.
  6. Z. Yang and W. Pan, Ionic liquids: Green solvents for nonaqueous biocatalysis, Enzyme Microb. Technol., 2005, 37, 19-28.