Exploitation of Soil and Rhizosphere Inhabiting Fungal Species for Biologically Active Secondary Metabolites
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EXPLOITATION OF SOIL AND RHIZOSPHERE INHABITING FUNGAL SPECIES FOR BIOLOGICALLY ACTIVE SECONDARY METABOLITES Ph. D Thesis By Saeed Ullah Khattak CENTRE OF BIOTECHNOLOGY AND MICROBIOLOGY UNIVERSITY OF PESHAWAR 2015 EXPLOITATION OF SOIL AND RHIZOSPHERE INHABITING FUNGAL SPECIES FOR BIOLOGICALLY ACTIVE SECONDARY METABOLITES Ph. D Thesis By Saeed Ullah Khattak A thesis submitted to the University of Peshawar for the fulfillment of the requirements for the degree of Doctor of Philosophy In Microbiology CENTRE OF BIOTECHNOLOGY AND MICROBIOLOGY UNIVERSITY OF PESHAWAR 2015 i EXPLOITATION OF SOIL AND KHIZOSPHERE INHABITING FUNGAL SPECIES FOR BIOLOGICALLY ACTIVE SECONDARY METABOLITES This thesis is submitted by Saeed UUah Kiiattak for the fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology Approved bv: ]r Prof. Dr, Ghosia Lutfullah Research Supervisor 2. A, Dr. Zafar Iqbal Research Co- supervisor Dr. Syed Tahir Abbas Shah (COMSATS Islamabad) External Examiner 4. Professor Dr. GhosiaLutfullah Director Centre of Biotechnology and Microbiology University of Peshawar ii ACKNOWLEDGEMENTS I express my humble and profound gratitude to Al-Mighty Allah, who enabled me to complete this task. I am overwhelmed with gratitude to our Holy Prophet Hazrat Muhammad (PBUH) who taught us to seek knowledge from cradle to the grave. I am extremely grateful to my supervisor, Professor Dr. Ghosia Lutfullah, Director Centre of Biotechnology and Microbiology, University of Peshawar, Pakistan for her valuable suggestions, guidance, motivation, support and affectionate environment which helped me a lot to complete this task successfully. I would like to extend my gratitude to my co- supervisor, Dr. Zafar Iqbal, Assistant Professor Department of Agricultural Chemistry, The University of Agriculture Peshawar, for all his help, sincere guidance and support throughout my research work. I would like to thank Professor Dr. Bashir Ahmad, Meritorious Professor Centre of Biotechnology and Microbiology, University of Peshawar, Pakistan who provided me the opportunity to enroll for PhD degree during his directorship. I cannot ignore the efforts of Dr. Nafes Bacha Assistant Professor Centre of Biotechnology and Microbiology, University of Peshawar, Pakistan for his help and guidance in starting and progression of my research. I will never forget the efforts of Dr. Abid Ali Khan my friend, lab fellow and now Assistant Professor at COMSATS Institute of Information Technology, Abbottabad, Pakistan for his help and motivation throughout my research. I would also like to extend my sincere thanks to Professor Dr. Hameed Ullah Shah, Chairman Department of Agricultural Chemistry, for allowing me for research work in his lab and providing me necessary facilities to conduct my research. I am extremely thankful to Dr. Azeem Khan, Chairman Department of Weed Science The University of Agriculture Peshawar for his cooperation and support during my PhD research. I am thankful iii to all the faculty members of Department of Weed Science for their support and help during my PhD research. I will surely extend my gratitude to Professor Dr. Hizbullah, Professor Department of Environmental Science University of Peshawar for his encouragement and guidance. I extend my thanks to the entire faculty of COBAM, supporting staff especially Ibrar Khan, for their patience and co–operation during my stay at the Centre. I will never forget the help of my lab fellows and friends who helped me in completion of this task. In last but not the least, I am really thankful to all my family members, my wife, my children, my brothers and sisters who always encouraged me and supported me during the completion of my PhD degree. Saeed Ullah Khattak iv AUTHOR’S DECLARATION It is declared that the overall research work presented in this thesis is the original work conducted by the author in accordance with University of Peshawar’s regulations for the requirements of Research Degree Program. This is the author’s original work and has never been previously submitted elsewhere for any kind of academic award. The views expressed in the thesis, belongs to the author. Date____20/8/15________ Signature_________________ v DEDICATION THIS HUMBLE EFFORT IS DEDICATED TO MY PARENTS (LATE) AND MY FAMILY AS WITHOUT THEIR SUPPORT IT WOULD NEVER BE POSSIBLE FOR ME TO COMPLETE THIS TASK vi TABLE OF CONTENTS ACKNOWLEDGEMENTS ............................................................................................................................... iii AUTHOR’S DECLARATION .................................................................................................................v DEDICATION ........................................................................................................................................ vi TABLE OF CONTENTS ...................................................................................................................... vii LIST OF FIGURES ............................................................................................................................. xiii LIST OF TABLES ............................................................................................................................... xvi LIST OF ABBREVIATIONS .............................................................................................................. xvii ABSTRACT .......................................................................................................................................... xxi Chapter 1 INTRODUCTION ....................................................................................................................1 1.1 Fungi as chemical industries ...............................................................................................................2 1.1.1 Aspergillus .......................................................................................................................3 1.1.1 Penicillium .......................................................................................................................................5 1.2 Aims and objectives............................................................................................................6 1.3 Socioeconomic benefits .....................................................................................................8 Chapter 2 REVIEW OF RELATED LITERATURE ........................................................................................... 10 2.1 Natural products and their importance ..............................................................................................10 2.2 Natural products classification .........................................................................................14 2.2.1 Polyketides .....................................................................................................................................14 2.2.1.1 Types of polyketides ...................................................................................................17 2.2.1.1.1 Linear polyketides ...................................................................................................18 2.2.1.1.2 Halogenated acetogenins .........................................................................................................18 2.2.1.1.3 Annonaceae acetogenins ..........................................................................................19 2.2.1.1.4 Macrolides and lactone polyketides ........................................................................19 2.2.1.1.5 Ansamycins and related polyketides ........................................................................................20 vii 2.2.1.1.6 Polyenes ...................................................................................................................21 2.2.1.1.7 Tetracyclines ............................................................................................................21 2.2.1.1.8 Angucyclines............................................................................................................................22 2.2.1.1.9 Polyether polyketides ..............................................................................................23 2.2.1.1.10 Aflatoxins ..............................................................................................................23 2.2.2 Terpenoids......................................................................................................................................24 2.2.2.1 Monoterpenoids or C10 terpenoids ..............................................................................25 2.2.2.2 Sesquiterpenoids or C15 terpenoids .............................................................................26 2.2.2.3 Diterpenoids or C20 terpenoids....................................................................................................27 2.2.2.4 Triterpenoids, Tetraterpenoids, Polyterpenoids and Meroterpenoids .......................28 2.2.3 Alkaloids ........................................................................................................................29 2.2.4 Non ribosomal peptides .................................................................................................................32 2.2.4.1 NRPS genes in fungi...................................................................................................34 2.2.4.2 Important catalytic NRPSs domains ...........................................................................35