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Process modeling of the lipase-catalyzed dynamic kinetic resolution of (R, S)-suprofen 2,2,2-trifluoroethyl thioester in a hollow-fiber membrane

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Abstract

A Candida rugosa lipase immobilized on polypropylene powder was employed as the biocatalyst for the enantioselective hydrolysis of (R, S)-suprofen 2,2,2-trifluorothioester in cyclohexane, in which trioctylamine was added as the catalyst to perform in situ racemization of the remaining (R)-thioester. A hollow-fiber membrane was also integrated with the dynamic kinetic resolution process in order to continuously extract the desired (S)-suprofen into an aqueous solution containing NaOH. A kinetic model for the whole process (operating in batch and feed-batch modes) was developed, in which enzymatic hydrolysis and deactivation, lipase activation, racemization and non-enantioselective hydrolysis of the substrate by trioctylamine, and reactive extraction of (R)- and (S)-suprofen into the aqueous phase in the membrane were considered. Theoretical predictions from the model for the time-course variations of substrate and product concentrations in each phase were compared with experimental data.

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Scheme 1
Scheme 2
Fig. 1
Fig. 2a–e
Fig. 3
Fig. 4a–e
Fig. 5
Fig. 6
Fig. 7

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Abbreviations

A :

membrane surface area (cm2)

(B):

trioctylamine concentration (mM)

(E):

effective enzyme concentration (mg cm−3)

(Et):

initial enzyme concentration (mg cm−3)

E*:

enantiomeric ratio, defined as k2AKmB/k2BKmA

eep:

enantiomeric excess for suprofen products

ees:

enantiomeric excess for thioester substrates

f1, f2:

functions defined in Eqs. 18 and 19

f3, f4:

functions defined in Eqs. 20 and 21 (mM h−1)

(H+):

hydrogen ion concentration (mM)

K d :

dissociation constant of (R)- or (S)-suprofen in the aqueous phase (mM)

K P :

partition coefficient of (R)- or (S)-suprofen between cyclohexane and the aqueous phase; in other words [(QB)/(QBW)]eq or [(QA)/(QAW)]eq

K w :

dissociation constant of water (mM2)

KmA, KmB:

Michaelis-Menten constant for (S)- or (R)-thioester (mM)

k h :

rate constant for the non-stereoselective hydrolysis of thioester (h−1)

k i :

interconversion constant for (R)- or (S)-thioester (h−1)

k over :

overall mass transfer coefficient for suprofen in the membrane (cm2 h−1)

k1, k2:

enzyme deactivation constants in the series mechanism (h−1)

k2A, k2B:

kinetic constant for (S)- or (R)-thioester in Michaelis-Menten kinetics (mM cm3 mg−1 h−1)

(Na+):

sodium ion concentration (mM)

(OH−):

hydroxide ion concentration (mM)

(QA), (QB):

concentrations of (S)- and (R)-suprofen in isooctane (mM)

(QA–W), (QB–W):

concentrations of ionized (S)- and (R)-suprofen in the aqueous phase (mM)

(QAW), (QBW):

concentrations of (S)- and (R)-suprofen in the aqueous phase (mM)

r :

fraction of enzyme activity for the intermediate lipase

(SA), (SB):

concentrations of (S)- and (R)-thioester in isooctane (mM)

t :

time (h)

VA, VB:

reaction rates for (S)- and (R)-thioesters (mM h−1)

VO, Vw:

volumes of the organic and aqueous phases (cm3)

XA, XB, Xt:

conversions of (S)-, (R)- and (R, S)-thioesters

eq:

at equilibrium

0:

initially

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Acknowledgements

The financial support from the Chinese National Science Council with Grant NSC90-2214-E-006-021 is appreciated.

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  1. Department of Chemical Engineering, National Cheng Kung University, Tainan, 70101, Taiwan

    L. W. Wang, Y. C. Cheng & S. W. Tsai

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  1. L. W. Wang
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  2. Y. C. Cheng
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  3. S. W. Tsai
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Correspondence to S. W. Tsai.

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Wang, L.W., Cheng, Y.C. & Tsai, S.W. Process modeling of the lipase-catalyzed dynamic kinetic resolution of (R, S)-suprofen 2,2,2-trifluoroethyl thioester in a hollow-fiber membrane. Bioprocess Biosyst Eng 27, 39–49 (2004). https://doi.org/10.1007/s00449-004-0379-8

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