In this chapter the main findings of the work described in this thesis, aimed at the development of a process for the production of enantiomerically pure epoxides by enzymatic kinetic resolution, are summarised. The work was carried out using an epoxide hydrolase originally isolated from the organism Agrobacterium readiobacter AD1 (van den Wijngaard et al., 1989). The scale-up of this biocatalytic reaction is complicated by the poor solubility of epoxides in water, enzyme inhibition by the produced diol, and enzyme instability under reaction conditions (Chapter 1). ...

Zie: Chapter 6

Baldascini, Helen Gabriela,

Baldascini, Helen Gabriela

University of Groningen

   University of GroningenBioreaction engineering for the kinetic resolution of racemic epoxides by epoxide hydrolaseBaldascini, Helen GabrielaIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2004Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Baldascini, H. G. (2004). Bioreaction engineering for the kinetic resolution of racemic epoxides by epoxidehydrolase. Groningen: s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019147DankwoordThe completion of this PhD thesis would not have been possiblewithout the support of many people during my time in Groningen. First of allI would like to thank Dick Janssen for taking over the supervision of thisPhD project and contributing greatly to it through endless enthusiasm andinvaluable suggestions. Participation in your group’s activities provided agreat opportunity for me to widen my academic knowledge and interests. Ihave learned a great deal from you, in particular thoroughness in scientificwriting.I thank Ton Beenackers for giving me the opportunity to come toGroningen to do this PhD, which has been a truly important learningexperience.This work was greatly enriched by all those working with epoxidehydrolase. I would like to thank Rick Rink for stimulating discussions onepoxide hydrolase structure/function and his profound knowledge on thesubject, Marco Nardini for his enthusiasm in the practical application ofepoxide hydrolase cross linked crystals; and Jeffrey Lutje Spelberg forhelping with all things chemical.For day to day lab support I thank Piet Wietzes for his ‘can do’attitude in solving problems with analytical equipment, Jaap Kingma formaking enzyme purification look so easy, Marc van Gelder and MarinusSuikerbuijk for assistance in GC analysis, Henriëtte Rozeboom for help inthe crystallisation of epoxide hydrolase, Jaap Broos for advice onbiophysical techniques, Anne for building an excellent stirred cell, MartijnOlde Weghuis for carrying out initial experiments with the stirred cell,Sandra Haan and Hilda Riemens for their assistance in administrative tasksduring submission of the thesis. I am also grateful to other scientists with whom I had the opportunityto collaborate and share ideas over the course of this PhD, in particular,Jeroen den Hollander and Adrie Straathof at the University of Delft.I would like to thank the members of the reading committee, Prof.Dijkhuizen, Prof. Heeres and Prof. Tramper, that approved this thesis.“Bedankt!” to all the members of the Janssen group for the pleasantatmosphere in the lab and the many gezellige koffies met taart and leukeborreltjes: Astrid, Bert, Erik, Esther, Geja, Inez, Jantien, Johan, Jolanda,Lixia, Marco, Mariël, Marko, Nanne, Simon, Tjibbe, Wouter and Wynand.148Jose Tijsen and Marijn Sipkema I remember for accompanying me in thosestrenuous circuit training sessions and keeping me informed about allchemical engineering events. A “muito obrigada” to Fatima: the endlesspreparations of Bacalhau dishes and our dinner time conversations reallyenlivened my last few months in Groningen. Outside the lab I would like to thank our friends in the expatcommunity for sharing and making the Groningen experience moreenjoyable. You may have wondered what I was doing all that time… now youknow (or perhaps not!).Above all, I thank my parents for giving me so much and asking solittle in return. Grazie mamma e papà per il vostro costanteincoraggiamento e sostegno. Alexia e Nathalie, grazie per il vostro senzodell’umorismo che mi ha regalato momenti di leggerezza in questo periodoimpegnativo. Finally, a big “grazie!” to Dan for always putting things intoperspective and for generally keeping me sane!HelenLondon, August 2004

Bioreaction engineering for the kinetic resolution of racemic epoxides by epoxide hydrolase

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