Amino acid transport in Penicillium chrysogenum in relation to precursor supply for betalactam
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1 University of Groningen Amino acid transport in Penicillium chrysogenum in relation to precursor supply for betalactam production Trip, Hein IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2005 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Trip, H. (2005). Amino acid transport in Penicillium chrysogenum in relation to precursor supply for betalactam production s.n. Copyright Other 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 the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:
2 Amino acid transport in Penicillium chrysogenum in relation to precursor supply for β-lactam production
3 Cover: sporulating Penicillium chrysogenum (obtained from Enius AG (Germany), website This work was carried out in the Molecular Microbiology Group of the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) of the University of Groningen, the Netherlands, and was financially supported by the European Community (grant no QLK3-CT ).
4 RIJKSUNIVERSITEIT GRONINGEN Amino acid transport in Penicillium chrysogenum in relation to precursor supply for β-lactam production Proefschrift ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op vrijdag 21 januari 2005 om 14:45 uur door Hein Trip geboren op 22 juni 1975 te Nieuw Buinen
5 Promotor : Beoordelingscommissie : Prof. dr. A.J.M. Driessen Prof. dr. O. P. Kuipers Prof. dr. L. Dijkhuizen Prof. dr. M. Veenhuis
6 Voorwoord Dat was het dan. Meer dan vier jaar aio geweest, resulterend in dit proefschrift. Rond de tijd dat ik afstudeerde, wist ik niet of ik wel aio zou willen worden. Ik heb het toch gedaan op advies van onder andere mijn begeleider van mijn eerste afstudeeronderwerp, Ted van der Lende. En ik heb er geen spijt van gekregen. Het was een mooie tijd waarin ik veel geleerd heb en mooie en nieuwe ervaringen heb gehad zoals bijvoorbeeld het publiceren van het eerste artikel. Dat het een geslaagde tijd was heeft voor een groot deel gelegen aan de omgeving waarin ik heb kunnen werken. Daarom wil ik een aantal mensen bedanken. In de eerste plaats Arnold, mijn promotor. Over je wetenschappelijke talent en kundigheid hoef ik niet meer uit te weiden, dat is al zo vaak gebeurd. Ik wil wel speciaal noemen dat ik het heel plezierig vond dat je altijd bereid was om te luisteren als ik ergens mee kwam, om me vervolgens een zetje in de goede richting te geven. Die toegankelijkheid heb ik erg gewaardeerd. Wil, door jou werd ik zeven jaar geleden in de moleculaire microbiologie vakgroep geïntroduceerd om een onderzoeksonderwerp te doen, de inleiding tot de aio-plaats twee jaar daarna. Melchior, bedankt voor de dagelijkse begeleiding en daarnaast voor het mogen verwerken van jouw werk in hoofdstuk 1 van dit proefschrift en je substantiële bijdrage aan hoofdstuk 3. Ik heb een hoop lol gehad in het lab, mede dankzij je gezonde relativering van alles wat te serieus genomen wordt. Dit geldt ook voor Jeroen, Paolo en Marta, mijn andere labgenoten. Het was fijn om met jullie in het lab te werken en bedankt voor jullie tolerantie wat betreft mijn muziekliefhebberij. Eli, Ana, Nico, Oscar, Piotr, Rasmus, Chris, René, Geert en alle anderen waarmee ik buiten het lab de zinnen verzet heb: ik hoop dat dit zal blijven gebeuren. Maartje, Job en papa, ik ben blij dat jullie er altijd zijn. Hein
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8 Contents Chapter 1 9 Introduction: Compartmentalization and transport in β-lactam antibiotics biosynthesis Chapter 2 42 Cloning and characterization of an aromatic amino acid and leucine permease of Penicillium chrysogenum Chapter 3 57 Uptake of the β-lactam precursor α-aminoadipate in Penicillium chrysogenum is mediated by the acidic and the general amino acid permease Chapter 4 79 PcMtr, an aromatic and neutral aliphatic amino acid permease of Penicillium chrysogenum Chapter 5 93 Random mutagenesis of PcDIP5 and selection for improved α-aminoadipate transport Chapter Summary and concluding remarks Chapter Nederlandse samenvatting References 123
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