TY - JOUR
T1 - Production of cephalexin in organic medium at high substrate concentrations with CLEA of penicillin acylase and PGA-450
AU - Illanes, A.
AU - Wilson, L.
AU - Altamirano, C.
AU - Cabrera, Z.
AU - Alvarez, L.
AU - Aguirre, C.
N1 - Funding Information:
This work was funded by Grants 1040748 and 1050303 from Fondecyt, Chile. The authors wish to thank Ms. Rosa Arrieta for her valuable analytical support.
PY - 2007/1/4
Y1 - 2007/1/4
N2 - The kinetically controlled synthesis of cephalexin in ethylene glycol was previously optimized at moderate substrate concentrations obtaining yields close to stoichiometric. A study is now presented on the production of cephalexin at very high substrates concentrations, up to 750 mM acyl donor, with immobilized and cross-linked enzyme aggregates (CLEA) of penicillin acylase. Since conversion yield close to 100% was already obtained, attention was given to productivity under the hypothesis that increasing substrates concentration will produce a substantial increase in productivity without reducing yield. An increase of 29 times in volumetric productivity and 4.5 times in specific productivity was obtained with PGA-450 with respect to the results obtained at moderate substrates concentrations (below 100 mM acyl donor). Volumetric productivity was lower for CLEA than for PGA-450, but specific productivity was almost the same for both. Sequential batch reactor operations were conducted to assess the biocatalyst operational stability and global productivity, considering one half-life as biocatalyst life cycle. Under such criterion, 40.1 and 135.5 g of cephalexin/g of biocatalyst were obtained for PGA-450 and CLEA, respectively. Yields remained close to 100% during the whole cycle. These are very good values which can be improved by optimizing the biocatalyst replacement criterion.
AB - The kinetically controlled synthesis of cephalexin in ethylene glycol was previously optimized at moderate substrate concentrations obtaining yields close to stoichiometric. A study is now presented on the production of cephalexin at very high substrates concentrations, up to 750 mM acyl donor, with immobilized and cross-linked enzyme aggregates (CLEA) of penicillin acylase. Since conversion yield close to 100% was already obtained, attention was given to productivity under the hypothesis that increasing substrates concentration will produce a substantial increase in productivity without reducing yield. An increase of 29 times in volumetric productivity and 4.5 times in specific productivity was obtained with PGA-450 with respect to the results obtained at moderate substrates concentrations (below 100 mM acyl donor). Volumetric productivity was lower for CLEA than for PGA-450, but specific productivity was almost the same for both. Sequential batch reactor operations were conducted to assess the biocatalyst operational stability and global productivity, considering one half-life as biocatalyst life cycle. Under such criterion, 40.1 and 135.5 g of cephalexin/g of biocatalyst were obtained for PGA-450 and CLEA, respectively. Yields remained close to 100% during the whole cycle. These are very good values which can be improved by optimizing the biocatalyst replacement criterion.
KW - CLEA
KW - Cephalexin
KW - Organic cosolvents
KW - Penicillin acylase
UR - http://www.scopus.com/inward/record.url?scp=33751189800&partnerID=8YFLogxK
U2 - 10.1016/j.enzmictec.2006.03.041
DO - 10.1016/j.enzmictec.2006.03.041
M3 - Article
AN - SCOPUS:33751189800
VL - 40
SP - 195
EP - 203
JO - Enzyme and Microbial Technology
JF - Enzyme and Microbial Technology
SN - 0141-0229
IS - 2
ER -