BESSICC, a COSMO‐RS based tool for in silico solvent screening of biocatalyzed reactions

Abstract

Many enzymatic reactions are near-equilibrium reactions. This often limits final yield and hence application of biocatalyzed processes in the industrial production. The most widely applied strategy to overcome this issue is solvent selection. It must be underlined that measuring the equilibrium position experimentally is a difficult and time-consuming procedure and any tool for predicting the solvent effect on the reaction equilibrium can be very valuable. The present work reports on the development of BESSICC, an algorithm to calculate the effect of medium composition on biocatalyzed reactions equilibrium. It is based on COSMO-RS calculation of activity coefficients of all the species in the reaction mixture and minimization of Gibbs free energy of the reaction. Starting from one single experimental measurement of the equilibrium position for a given biocatalyzed reaction it can predict the yield of the reaction in any other solvent or solvent mixture. Predictions are accurate, the errors of prediction are in average below 25% for the esterification of dodecanoic acid with menthol and below 65% for esterification of 1-dodecanoic acid with 1-dodecanol. The best predictions show an error well below 5%.

Thermodynamics of Bioreactions

“…If the pure-component standard state is used for all reacting agents in a reaction, K a must be determined from the mole fractions, x i , and the generic activity coefficients of the reacting species, γ i , which are 1 for the pure-component state. To avoid confusion with K a from Equation 5, some researchers (30,31) have renamed the equilibrium constant K th . Using x i · γ i = m i · γ m,i , mole fractions can be replaced by molalities, which can then be used as concentration units:…”

“…By using Equation 1, tools from biochemistry, such as thermodynamic feasibility analysis, have been applied to calculations for metabolic networks (26,27,30,31). Mavrovouniotis (27) and Vojinovic & von Stockar (32), as well as Maskow & von Stockar (33), analyzed glycolysis using experimental nonequilibrium concentrations of the reacting agents and R g 0 data, which were available from a previous study (34).…”

“…Two standard states are commonly used for the reacting agents: the standard-state pure component and the standard-state hypothetical ideal solution. The first is usually applied to chemical reactions and is rarely used for bioreactions (30,31). As most biological reactions are performed at low concentrations of reacting agents, their thermodynamic behavior is quite different from the pure-component standard state.…”

“…According to Equations 5 and 8, K a and K th values are accessible using measured equilibrium molalities (→ K m ) and the activity coefficients of the reacting agents, γ i,m or γ * i,m . The latter depend on the concentrations of the reacting agents and the system composition and must be estimated using a thermodynamic model (30,31,47,48). For an infinite dilution of all reacting agents, K γ * becomes truly 1.…”

“…Lipases are particularly worthwhile catalysts for esterification reactions, as the presence of a high amount of water dramatically decreases product yield due to equilibrium limitations. Thus, esterifications are usually performed in solvents other than water (e.g., in alcohols) (30,31,117).…”