Mathematical analysis of two‐phase mass transfer in a batch reactor for the chemical transformation of a steroid

Abstract

A reactor is described for the conversion of the slightly water-soluble steroid testosterone (T) to 4-androstene-3, 17-dione (4-AD) by enzyme in the presence of excess cofactor. Since the enzyme is subject to substrate inhibition, reaction rates are strong functions of aqueous substrate concentration. High concentrations of the substrate, testosterone, per unit reactor volume are maintained within poly(dimethylsiloxane) beads that are suspended in the aqueous enzyme solution. Mass transfer (controlled by bead size, polymer to water volume ratio, enzyme loading) is used to control the degree and rate of conversion. The reactor dynamics are predicted over a wide range of reaction conditions. The product steroid is recovered in the polymeric beads from the enzyme solution.

Manipulation of Bulk Reactions in Multiphase Systems by the Use of Microheterogeneous Media

“…In this region the reaction rates are directly proportional to the substrate concentrations. Thus, there exists an optimal radius, for MT kinetics, as was ® rst suggested by Pereira et al 11 . It may also be noticed that larger particles offer greater internal resistance to diffusion so that the substrate concentration at the solid-liquid interface, C si /m s declines more rapidly with time for a large particle as compared to a small one.…”

“…The use of polymeric solids as substrate reservoirs, in lieu of organic solvent drops, was therefore proposed in order to avoid the danger of enzyme denaturation and also to provide for easier handling compared to oil-in-water emulsions. Pereira et al 11 actually studied the strategy of loading the sparingly water-soluble substrate on to a hydrophobic polymer and the subsequent suspension of these loaded polymer beads in the aqueous enzyme solution. These workers examined the conversion of testosterone (17b-hydroxyandrost-4-ene-3-one) to androst-4-ene-3,17-dione by the enzyme 3,17b-hydroxysteroid dehydrogenase (recovered from Pseudomonas testosteroni).…”

“…R 2 /D s as well as the batch time scale. These conditions are valid for all the computations carried out in this study and are required to be satis® ed so that the boundary condition stated by equations (11) and (12) change insigni® cantly over the period h c .…”

“…Unlike, Bhasin et al 7 who exclusively used an oil phase as the substrate reservoir and Pereira et al 11 who used only polymer beads, a more optimal strategy may be to use both oil and solid reservoir phases in combination. For instance, it may be more feasible to add an emulsi® ed phase to the system in order to attain greater conversions within a given time than to fabricate particles of a size different from those already available.…”

Mathematical analysis of solid–liquid mass transfer in a batch reactor for the enzymatic transformation of testosterone to 4AD

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Abstract: A previous mathematical analysis of mass transfer in a two-phase (solid±liquid) batch reactor for enzymatic transformation of testosterone to 4AD (Pereira et al, 1987) is extended to incorporate the effect of convective mixing. The results of the analysis showed that for a given enzyme loading, the mass transfer resistance in the solid (a function of the bead size) and the intensity of convective mixing (as embodied in the mass transfer coef®cient) are two parameters that can be varied such that the overall mass transfer rate from the solid to the liquid phase ensures optimal reactor performance.

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