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The Function of Pufq in the Regulation of Bacteriochlorophyll Biosynthesis in Rhodobacter Capsulatus

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The Function of Pufq in the Regulation of Bacteriochlorophyll Biosynthesis in Rhodobacter Capsulatus The Function of PufQ in the Regulation of Bacteriochlorophyll Biosynthesis in Rhodobacter capsulatus Himani Rajeshwar Utkhede B.Sc. Simon Fraser University, 200 1 THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS OF THE DEGREE OF MASTER OF SCIENCE in the Department of Molecular Biology and Biochemistry O Himani R. Utkhede 2004 SIMON FRASER UNIVERSITY March, 2004 All rights reserved. This work may not be reproduced in whole or in part, by photocopy or other means, without permission of the author. Approval I Name: Himani R. Utkhede Degree: Master of Science Title of Thesis: The Function of PufQ in the Regulation of Bacteriochlorophyll Synthesis in Rhodobacter capsulatus. Examining Committee: Dr. W.S. Davidson, Chair Dr. William R. Richards, Senior Supervisor Professor Emeritus, Molecular Biology and Biochemistry Simon Fraser University Dr. Michel Leroux, Supervisor Assistzt Prcfessor, ?v!s!ec.dzr Eic!ca.;- - 2~2L3.icche~isty Simon Fraser University Dr. Erika Plettner, Supervisor Assistant Professor, Chemistry Simon Fraser University Dr. Lynne Quarmby, Internal Examiner Assistant Professor, Biology Simon Fraser University Date Approved: Partial Copyright Licence The author, whose copyright is declared on the title page of this work, has granted to Simon Fraser University the right to lend this thesis, project or extended essay to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational institution, on its own behalf or for one of its users. The author has further agreed that permission for multiple copying of ths work for scholarly purposes may be granted by either the author or the Dean of Graduate Studies. It is understood that copying or publication of this work for financial gain shall not be allowed without the author's written permission. The original Partial Copyright Licence attesting to these terms, and signed by this author, may be found in the original bound copy of this work, retained in the Simon Fraser University Archive. Bennett Library Simon Fraser University Bumaby, BC, Canada Abstract I The pufQ gene of Rhodobacter capsulatus is essential for the synthesis of functional amounts of the photosynthetic apparatus. Here, we present evidence for the involvement of the pufQ gene product in the regulation of two enzymes in the bacteriochlorophyll biosynthesis pathway in response to changing oxygen tensions. A strain (HUP35A) bearing a chromosomal point mutation in the pufQ gene synthesizes more bacteriochlorophyll than JSOl and JS02, but still considerably less than wildtype R. capsulatus. Normally, the activities of HemB and HemZ in the wildtype strain were increased by about two-fold upon transfer from aerobic to semiaerobic growth conditions. Disruption of the pufQ gene, either by chromosomal knockout or point mutation, leads to an incomplete induction of the enzyme specific activities of both Hem2 and HemB upon transfer to semiaerobic growth conditions. Therefore, it was concluded that the proline35alanine substitution appears to have an effect on the functionality of PufQ under photosynthetic growth conditions. We also present evidence that OW227 is an aerobic repressor of hem2 transcription and a hypothetical model is proposed for the function of PufQ in the inactivation of the OW227 repressor on hem2 transcription under photosynthetic conditions. The conversion of ALA acid to PBG is the second step in the bacteriochlorophyll biosynthesis pathway, and is catalyzed by HemB. A complete kinetic analysis of HemB was undertaken and the effect of two porphyrins and two porphyrinogens on HemB specific activity was also determined. Here, we present evidence that the two porphyrinogens, Coprogen and Urogen, successive intermediates in the early pathway of bacteriochlorophyll biosynthesis, act in the manner of a potent two-fold intermediate feedback inhibition on HemB activity. Both of these porphyrinogens exhibit a mixed-type inhibition of HemB. Coprogen demonstrated K, and KI values of 3.05 pM and 13.6 pM, respectively, while Urogen demonstrated Ki and KI values of 8.2 pM and 7.0 pM, respectively. To Mom and Baba Acknowledgements Many people have been a part of hygraduate education, as friends, teachers, and colleagues. Dr. Richards, first and foremost, has been all of these. He is by far, the best advisor and teacher I could have wished for. With his enthusiasm, his inspiration, and his great efforts to explain things clearly and simply, he helped to make biochemistry fun for me. Throughout my thesis-writing period, he provided encouragement, sound advice, good teaching, and lots of great ideas. Thanks are also due to Dr. Leroux and Dr. Plettner for their help and guidance during the course of this investigation. In SSB, I was sourrounded by knowledgeable and friendly people who helped me daily. Dan Chinnapen, Darrell Bessette, Bari Zahedi, Carlo Sankar, Betty Chung, Kris Palma, Leslie Mitchell, Ashvinder Bhogal, Amit Goel, Carlo Artieri, Etienne Mahe, Teresa Pires, Jillian Smith, Koman Joe and Minna Roh, were each a great help in their own way. A special thanks goes to Darrell, Carlo S., and Carlo A. for their humour. Thanks also to Bari and Minna for their advice in academics as well as life. In addition to the people in SSB, I was lucky enough to have the support of many good friends at the Old Spaghetti Factory, including Nicole Andrews, Nicole Thibeault, Sonya Westgeest, Lisa Kabesh, Jessica Becker, Cypris Nichol, Ryan Mountain, Chris Inglis, Ross Gordon, Kevin Morrow, Travis Boa, and Larry Reimer. Life in graduate school would not have been the same without the Old Spaghetti Factory, and therefore, I must extend a great big thank you to the restaurant for continued financial and nutritional support. Finally, I would like to thank those who are most important to me, whose presence helped make the completion of my graduate work possible. These are Melita and James Irving, the two best roommates and friends one could have. They were a fantastic source of practical advice and information, laughter, as well as being happy to be the first to hear my outrage or glee at the day's current events. I also am thankful to Dan Chinnapen, for coffee breaks, his computer support, and brightening all my days in MBB. Most of all, I would like to thank my family, and especially my parents, for their absolute confidence in me. v Table of Contents .. Approval .................................................A ........................................................................ ...11 Abstract ............................................................................................................................111 Dedication ..........................................................................................................................iv Acknowledgements ............................................................................................................v Table of Contents ........................... .................................................................................vi List of Tables .................................................. ................................................................x List of Figures ....................................................................................................................xi... List of Abbreviations .....................................................................................................xlll 1.0 Introduction ....................................................................................................................1 1.1 Bacterial Photosynthesis .............................................................................................1 1.1.1 Light Harvesting Complex I ................................................................................3 1. 1.2 Light Harvesting Complex I1 ............................................................................... 4 1.1.3 Reaction Center Complex ....................................................................................5 1.1.4 The Mechanism of Bacterial Photosynthesis .......................................................6 1.2 The Biosynthesis of Bacteriochlorophyll a and Carotenoids .....................................8 1.2.1 Enzymes and Intermediates Shared by the Heme and Bacteriochlorophyll a Biosythetic Pathways .................................................... 9 1.2.1.1 Formation of Porphobilinogen by Porphobilinogen Synthase .......................9 1.2.1.2 Formation of Protoporphyrinogen IX by Coproporphyrinogen I11 Av;rlocrn 17 VILIL'CIUV ........................................................................................................* - 1.2.2 Biosythesis of Bacteriochlorophyll a from Protoporphyrin IX .........................12 1.2.3 Biosynthesis of Carotenoids ..............................................................................16 1.3 Genes Required for Photosynthesis ......................................................................... 17 1.3.1 The Photosynthetic Gene Cluster ....................................................................... 17 1.3.2 Genes Outside the Photosynthetic Gene Cluster ............................................... 21 1.4 The Physiological Regulation of the Bacterial Photosynthetic Membrane Formation ............................................... ...........................................................23 1.5 Processing ofpuf Operon mRNA
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