**2.7. Enzyme reactions in solvent-free medium (SFM)**

Enzymatic catalysis in solvent-free medium (SFM) has attracted considerable interest in the recent years [90]. It used as an efficient approach to the synthesis of natural products, pharmaceuticals and food ingredients. Under nonaqueous conditions, the industrial utility of enzymes can be improved, recovery of product and enzyme is eased, and the ability to catalyze reactions that are not favorable in aqueous solutions [91]. However, it would be technically beneficial if the enzymatic reactions were performed in mixtures of substrates in the absence of solvents. Lipase-catalyzed PL has been extensively studied in systems using organic solvents; however, if such a process is intended to be used in the food industry, it is preferred to develop solventfree systems. The downside of organic solvents is that they are expensive, toxic and flammable and their use involves higher investment costs to meet safety requirements [80]. On the other hand, solvent-free systems, which are a simple mixture of reactants and the biocatalyst, present the advantages of using nearly nonaqueous organic solvents while offering greater safety, reduction in solvent extraction costs, increased reactant concentrations and consequently higher volumetric productivity defined as kg product per unit of reactor volume [53, 80].

Phenolic lipids have been received increasing attention in the food area, since they are a good way for providing nutraceutical FA to consumers. Hong et al. [47] studied the esterification of vanillyl alcohol with conjugated linoleic acid under vacuum in solvent-free system. Further studies on the enzymatic synthesis of structured phenolic lipids in SFM have also been conducted by [34, 44, 92]. In these studies, phenolic acids were esterified with fatty acids resulted in the formation of more lipophilic constituents that can be used as a nutraceutical product. In addition, feruloylated mono- and diacylglycerols were synthesized in SFM using *C. antarctica* lipase, and the yield was 96% [92].

Lipase-catalyzed synthesis in SFM has a number of advantages as compared to that in OSM, including the use of a smaller reaction volume, maximization of substrate concentration and with no additional solvent recovery. In addition, downstream processing is easier as fewer purification steps are required providing significant cost savings, as well as toxic organic solvents are completely avoided (clean conversions), and an increase in the volumetric productivity can be achieved [80]. However, there are some problems with the use of SFM, mainly, the high viscosity of the medium as well as the production of high amounts of glycerol, free FAs as by-products. These by-products affect the reaction equilibrium and limit the mass transfer rate [93]. Thus, the development of a bioprocess for the lipase-catalyzed synthesis in SFM is of major interest but with great challenge.
