Continuous Countercurrent Extractive Biocatalysis in Aqueous Surfactant Two‐Phase Systems

Abstract

To evaluate the possibility of performing extractive biocatalysis in continuous mode, the hydrolysis of penicillin G in a micellar solution containing the nonionic surfactant Tergitol NP‐7 was chosen as model system. While the product phenylacetic acid distributes into the micellar phase, 6‐aminopenicillanic acid moves preferably into the aqueous phase. The yield in the continuous multi‐step process was higher in comparison to equivalent batch systems. Overall, the results demonstrate the suitability of aqueous surfactant two‐phase systems for continuous biocatalytic reactive extraction processes.

Reactive Separations for In Situ Product Removal of Enzymatic Reactions: A Review

“…Therefore, organic solvents can be categorized according to their polarity into three groups: The biocompatibility in polar solvents is low (logP i o/w < 2), adequate in solvents with 2 < logP i o/w < 4, and high in non-polar solvents (logP i o/w > 4) [153]. In contrast, different types of ATPS, like polymer/polymer [156] and polymer/salt [156][157][158] as well as special forms like micellar systems [17,159] and aqueous/ionic liquid (IL), showed generally fewer negative effects on enzymes, which can be explained by their high water contents.…”

“…The most commonly named example is the hydrolysis of penicillin G (PenG) to 6-aminopenicillanic acid and phenylacetic acid (PAA) ( Fig. 14) and is described with aqueous/organic systems [172][173][174] but also with aqueous/IL [175] as well as aqueous micellar two-phase systems (AMTPS) [17,159,176,177], which are a special form [133,134,146,169,190,191] steroids steroids (dehydrogenated) homogeneous / batch heterogeneous / batch reversed micelles -CTAB, octane, hexanol [192] [194] of ATPS formed by nonionic surfactants. Further examples are given in Tab.…”

“…With regards to the acid dissociation constant (pK a of penicillin G is 2.73 [178] and for phenylacetic acid 4.3 [179]), it is observable that the dissociation of penicillin G even at low pH values is higher in comparison to that of phenylacetic acid. With increasing pH (higher dissociation) the partition coefficients decrease and the partitioning of phenylacetic acid into the extraction phase is more favorable [17,180].…”

“…Moreover, den Hollander et al [174] described a countercurrent mixer-settler for the application of a quasi-continuous process. In contrast to an aqueous/organic system, Ritter and Smirnova [17] examined an aqueous micellar two-phase system (AMTPS), containing a phosphate buffer and the nonionic surfactant Tergitol NP-7 to perform a so-called cloud point extraction. By increasing the surfactant concentration above the critical micelle concentration, micelles are formed due to the amphiphilic character of the surfactant.…”

“…For example, extractive biocatalysis and reactive extraction both combine extraction with reaction. In the case of extractive biocatalysis the reaction equilibrium is shifted by in situ product removal to increase the yield of the reaction [17,18], whereas in reactive extraction an extractant that reacts with the solute is used to increase the selectivity and capacity of a solvent for the extraction [4,19,20]. Of course, reactive extraction can be used to perform extractive biocatalysis, but each term describes a different method of process intensification [4,21].…”