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Two Methylketone Biosynthetic Enzymes from Wild Tomatoes

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Two Methylketone Biosynthetic Enzymes from Wild Tomatoes Two methylketone biosynthetic enzymes from wild tomatoes By Geng Yu A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Molecular, Cellular and Developmental Biology) in the University of Michigan 2013 Doctoral Committee: Professor Eran Pichersky, Chair Professor Ursula Jakob Professor Jianming Li Professor Ronald W. Woodard © Geng Yu 2013 Dedication To My family for their sacrifice and love ii Acknowledgements I would like to express my sincere thanks to Dr. Eran Pichersky for his tremendous support and guidance throughout my Ph.D study. This dissertation would not be possible without the numerous hours he spent on reviewing and editing my writing. He has given me countless constructive suggestions to make my research progress quickly, the freedom to go to the conferences of my choice and the logic training for me to correctly analyze even the negative results and work more efficiently. I would also like to thank my thesis committee Drs. Ursula Jakob, Jianming Li, Ronald W. Woodard for their advice and comments during my doctoral research. I enjoy my working experience with the current and previous Pichersky lab members and also the seminar discussions I had with the 4th floor plant research lab members. I want to thank specially the postdocs I have directly worked with: Drs. Ines Shauvinhold, Thuong Nguyen and Nazmul Bhuiyan, for their guidance and help at the beginning stage of my Ph.D study. Vassiliki Falara, Dagan Hammar, Yuki Matsuba, and Reza Sohrobi have made valuable contributions to my oral defense talk. My thanks also go to my collaborators: Dr. Anthony L. Schilmiller in Robert L. Last lab and Dr. Yongxia Guo in Joseph Noel lab who have worked with me on two different manuscripts. Also, the department of Molecular, Cellular and Developmental Biology has a fully supportive group of staff, including Mary Carr, Kelly Campbell, Sheila Dunn, Diane Durfy, Jacqueline Glebe, Edward Grant, Gary Phillips, Laura Moggo and Gregg Sobocinski, who provided various help in different ways during my Ph.D. study. I also want to thank iii the members in our self-organized student-seminar group who helped to improve the oral presentation skill before my prelim and oral defense talks. Finally, I would like to express my appreciation to my mother Liping Zhang, who had lost my father Tingqi Yu just one year before I was admitted to graduate school but still made the sacrifice to let me study abroad. In addition, my wife Jingya Wang has made great support for my study here. Their love and support have made my study in US much easier. iv Table of contents Dedication ............................................................................................................... ii Acknowledgements ................................................................................................ iii List of Figures ...................................................................................................... xiv List of Tables ...................................................................................................... xvii Abstract .............................................................................................................. xviii Chapter 1 Introduction ......................................................................................... 1 1.1 BIOLOGICAL OCCURRENCE AND FUNCTIONS OF METHYLKETONES ...................................................................................................... 1 1.1.1 Definition of methylketones and the scope of this research ................ 1 1.1.2 Methylketone occurrence and function in mammals .......................... 1 1.1.3 Methylketone occurrence and function in insects ............................... 2 1.1.4 Methylketone occurrence and function in microbes ........................... 3 1.1.5 Methylketone occurrence and function in plants ................................ 3 1.2 BIOSYNTHESIS OF METHYLKETONES IN DIFFERENT ORGANISMS ................................................................................................................. 4 1.2.1 Methylketone biosynthesis in mammals ............................................. 4 v 1.2.2 Methylketone biosynthesis in insects .................................................. 6 1.2.3 Methylketone biosynthesis in some fungi and bacteria species .......... 6 1.2.4 Methylketone biosynthesis in plants ................................................... 8 1.3 FATTY ACID BIOSYNTHESIS IN PLANTS ........................................ 9 1.4 TRICHOME STUDY .............................................................................. 11 1.4.1 Introduction of trichomes .................................................................. 12 1.4.2 Chemicals in glandular trichomes ..................................................... 12 1.4.3 Biological functions of trichomes ..................................................... 13 Chapter 2 Multiple biochemical and morphological factors underlie the production of methylketones in tomato trichomes ............................................................ 15 2.1 ABSTRACT ............................................................................................ 15 2.2 INTRODUCTION ................................................................................... 16 2.3 RESULT .................................................................................................. 19 2.3.1 Morphological and Chemical Analyses of Interspecific Populations Derived from Crosses between the Cultivated Tomato and S. habrochaites f. sp. Glabratum 19 2.3.2 Association between Candidate Genes, Trichome Characteristics, and MK Content 24 2.3.3 Transcriptome Analysis of Trichomes from Bulked Segregants ...... 27 2.3.4 MKS2 Shares Sequence Identity with Hotdog-Fold Thioesterases .. 29 vi 2.3.5 MKS2 Is Associated with MK Content and Reveals an Epistatic Interaction with MKS1 ............................................................................................. 30 2.3.6 Heterologous Expression of MKS2 in Escherichia coli .................... 34 2.4 DISCUSSION ......................................................................................... 36 2.4.1 Developmental and Biochemical Connection in MK Synthesis ....... 36 2.4.2 The Genetic Basis for MK Biosynthesis in S. habrochaites f. sp. glabratum 37 2.4.3 The Role of MKS1 and MKS2 in MK Biosynthesis .......................... 39 2.5 CONCLUSION ....................................................................................... 42 2.6 MATERIALS AND METHODS ............................................................ 42 2.6.1 Plant Material, and Interspecific F2 and Backcross Populations ...... 42 2.6.2 Volatile Analysis ............................................................................... 43 2.6.3 Morphology Indexes ......................................................................... 43 2.6.4 Genotyping ........................................................................................ 43 2.6.5 HRM Genotyping .............................................................................. 44 2.6.6 Transcriptome Analysis ..................................................................... 44 2.6.7 qRT-PCR ........................................................................................... 45 2.6.8 Sequence Analysis............................................................................. 46 2.6.9 Statistical Analysis ............................................................................ 46 vii 2.6.10 Isolation of Full-Length ShMKS2 and SlMKS2 cDNAs and Expression in E. coli ................................................................................................. 47 2.6.11 Headspace Analysis of Spent Media of E. coli Cultures Expressing ShMKS2 and SlMKS2 ................................................................................................ 47 2.6.12 Homology Modeling ....................................................................... 48 Chapter 3 Enzymatic functions of wild tomato methylketone synthases 1 and 2 49 3.1 ABSTRACT ............................................................................................ 49 3.2 INTRODUCTION ................................................................................... 50 3.3 RESULTS................................................................................................ 53 3.3.1 Genes encoding MKS1 in Solanum lycopersicum and S. habrochaites glabratum 53 3.3.2 Genes encoding MKS2 in S. lycopersicum and S. habrochaites glabratum 56 3.3.3 Subcellular localization of ShMKS2 ................................................. 58 3.3.4 Expression of ShMKS1 and ShMKS2 in E. coli and production of methylketones 60 3.3.5 In vitro decarboxylase activity assays for ShMKS1 and ShMKS2 ... 64 3.3.6 In vitro thioesterase activity assays for ShMKS1 and ShMKS2 ....... 65 3.4 DISCUSSION ......................................................................................... 66 3.4.1 Enzymatic activities of ShMKS1 and ShMKS2 ............................... 66 viii 3.4.2 The mature ShMKS2 protein is localized to the plastids and is likely to hydrolyze 3-ketoacyl-ACP substrates ................................................................... 69 3.4.3 Evolution of ShMKS1 and ShMKS2 ................................................ 70 3.5 MATERIALS AND METHODS ............................................................ 72 3.5.1 Bioinformatics ..................................................................................
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