title: Process design for enzymatic adipyl-7-ADCA hydrolysis.
abstract: Adipyl-7-ADCA is a new source for 7-aminodeacetoxycephalosporanic acid (7-ADCA), one of the substrates for antibiotics synthesis. In this paper, a novel process for enzymatic 7-ADCA production is presented. The process consists of a reactor, a crystallization step, a membrane separation step, and various recycle loops. The reactor can either be operated batch-wise or continuously; with both types of processing high yields can be obtained. For batch reactors chemical degradation of 7-ADCA can be neglected. For continuous reactors, chemical stability of 7-ADCA is a factor to be taken into account. However, it was shown that the reaction conditions and reactor configuration could be chosen in such a way that also for continuous operation chemical degradation is not important. Downstream processing consisted of crystallization of 7-ADCA at low pH, followed by a nanofiltration step with which, at low pH, adipic acid could be separated from adipyl-7-ADCA and 7-ADCA. The separation mechanism of the nanofilter is based on size exclusion combined with charge effects. Application of this filtration step opens possibilities for recycling components to various stages of the process. Adipic acid can be recycled to the fermentation stage of the process while both adipyl-7-ADCA and 7-ADCA can be returned to the hydrolysis reactor. In this way, losses of substrates and product can be minimized.
authors.affiliation: Department of Agrotechnology and Food Sciences, Food and Bioprocess Engineering Group, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. karin.schroen@algemeen.pk.wau.nl
authors.forename: Catharina Gerarda Petronella Henrica
authors.initials: CG
authors.lastname: Schroën
authors.forename: Vincent Adriaan
authors.initials: VA
authors.lastname: Nierstrasz
authors.forename: Rouke
authors.initials: R
authors.lastname: Bosma
authors.forename: Zwaantje Johanna
authors.initials: ZJ
authors.lastname: Dijkstra
authors.forename: Emilius Johannes Albertus Xavierius
authors.initials: EJ
authors.lastname: VandeSandt
authors.forename: Hendrik Harmen
authors.initials: HH
authors.lastname: Beeftink
authors.forename: Johannes
authors.initials: J
authors.lastname: Tramper
mesh_terms: D000272:Adipates / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000378:metabolism*; D019149:Bioreactors; D001709:Biotechnology / Q000379:methods*; D002511:Cephalosporins / Q000096:biosynthesis* / Q000378:metabolism*; D003460:Crystallization; D004800:Enzymes, Immobilized / Q000378:metabolism; D005374:Filtration; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D000272:Adipates; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004800:Enzymes, Immobilized; C029900:adipic acid; C014320:7-aminodesacetoxycephalosporanic acid