Screening of organic solvents for bioprocesses using aqueous-organic two-phase systems

Abstract

The application of conventional organic solvents has been essential in several steps of bioprocesses in order to achieve sufficient economic efficiency. The use of organic solvents is frequently used either to partly or fully replace water in the reaction medium or as a process aid for downstream separation. Nowadays, manufacturers are increasingly requested to avoid and substitute solvents with hazardous potential. Therefore, the solvent selection must account for potential environmental hazards, health and safety problems, in addition to fulfilling the ideal characteristics for application in a process. For the first time, criteria including Environment, Health and Safety (EHS), as well as the technical requirements for reaction and separation have been reviewed, collected and integrated in a single organic solvent screening strategy to be used as a guideline for narrowing down the list of solvents to test experimentally. Additionally, we have also included a solvent selection guide based on the methodology developed in the Innovative Medicines Initiative CHEM21 (IMI CHEM21) project and applied specifically to water-immiscible solvents commonly used in bioprocesses.

Bioproduction of High-Concentration 4-Vinylguaiacol Using Whole-Cell Catalysis Harboring an Organic Solvent-Tolerant Phenolic Acid Decarboxylase From Bacillus atrophaeus

“…The solvent screening for the biphasic reaction was carried out in a biphasic system containing a Na 2 HPO 4 -citric acid buffer containing 200 mM of FA and different organic solvents for 2 and 6 h. As shown in Figure 4, the highest molar conversion yield (100%) of 4-VG was obtained in 1-octanol after 6 h of reaction, followed by n -octane, whose conversion yield reached up to 95%. Moreover, from safety, health, and environmental protection perspectives, 1-octanol is preferable to the other organic solvents tested (Grundtvig et al, 2018). Therefore, 1-octanol was selected as the organic solvent used in the subsequent experiments.…”

“…Yang et al (2009) reported that 21.3 g/L (141.9 mM) of 4-VG (95% conversion yield) was obtained by using E. coli harboring a FA decarboxylase from B. pumilus in 1L of an octane–aqueous two-phase system. These issues such as low yield and product concentrations are mainly caused by the toxicity of the substrate, product, and organic solvents and enzymatic inactivation (Tomek et al, 2015; Grundtvig et al, 2018). Although water-immiscible organic solvents were used in the biphasic system, trace solvents dissolved in the aqueous phase may have serious inhibitory effects on the biocatalysts (Doukyu and Ogino, 2010).…”

A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ‐Lactones

“…We therefore initiated our enzyme studies by surveying a panel of commercially available KREDs from Codexis Inc. against ketone 1 a for reduction and DKR activity (see electronic Supporting Information for screening details). The enzyme KRED‐P2‐C02 handily afforded γ‐lactone 2 a and was subsequently subjected to a broader selection of biphasic solvent conditions (Figure ) . Scale‐up of the screening hits found that, with minor additional optimization, biphasic solvent conditions with a clear partition between organic and aqueous phases predominated.…”

Polymersomes as Nanoreactors Enabling the Application of Solvent‐Sensitive Enzymes in Different Biphasic Reaction Setups

“…Furthermore, enzyme recovery is eased, reaction equilibria can be shifted toward the desired products and enantioselectivity is enhanced for several enzymes. [ 1,2 ]…”