0207 KUFA KUFA the marine marine the of stipitatus associated fungus associated - RECURSOS MARINHOS RECURSOS - Noinart MESTRADO MAR DO CIÊNCIAS secondary metabolites Bioactive culture the from sponge Talaromyces Jidapa M 2017 Jidapa Noinart. Bioactive secondary metabolites from the culture of the marine sponge-associated fungus Talaromyces stipitatus KUFA 0207 M.ICBAS 2017 Bioactive secondary metabolites from the culture of the marine sponge-associated fungus Ta l a ro my c e s stipitatus KUFA 0207 Jidapa Noinart INSTITUTO DE CIÊNCIAS BIOMÉDICAS ABEL SALAZAR JIDAPA NOINART BIOACTIVE SECONDARY METABOLITES FROM THE CULTURE OF THE MARINE SPONGE – ASSOCIATED FUNGUS TALAROMYCES STIPITATUS KUFA 0207 Dissertation for applying to the degree of Master in Marine Sciences – Marine Resources, as submitted to the institute of Biomedical Sciences Abel Salazar of the University of Porto. Supervisor – Professor Doutor Anake Kijjoa Category – Full Professor Affiliation – Institute of Biomedical Sciences Abel Salazar of the University of Porto. BIOACTIVE SECONDARY METABOLITES FROM THE CULTURE OF THE MARINE SPONGE-ASSOCIATED FUNGUS TALAROMYCES STIPITATUS KUFA 0207 Acknowledgement First of all, I would like to express my sincere gratitude to all the people who have accompanied me during my Master study journey in the University of Porto. To my respectful supervisor, Professor Dr. Anake Kijjoa who gave me the golden opportunity to do this project and study in the University of Porto. He does not only provide me valuable guidance and help me in studying and doing thesis, but also supports and encourages me to have the best successful work during my Master study. Also, Dr. Suradet Buttachon who always gives me help and guidance in my lab works. To Professor Dr. Eduardo Rocha, Director of the Master’s program in Marine Sciences and Marine Resources of Institute of Biomedical Sciences Abel Salazar (ICBAS) for accepting me to study in this program. Thank you to all the technicians and colleages in my laboratory, Mrs. Júlia Bessa, Miss Sónia Santos, Mrs. Isabel Silva, War War May Zin, Decha Kumla and all friends, for their supports and friendship in my daily life. To Associate Professor Dr. Poonpipope Kasemsap who always supports and encourages me to study in this prestigious university, University of Porto and Dr. Tida Dethoup who always supports me by providing the materials for this study. Finally, I would like to express my special thanks to the ALFABET project of the Erasmus Mundus Action 2 Scholarship and its coordinators who give me invaluable opportunities to study in the University of Porto. This chance allows me to extend my knowledges as well as gaining good experiences. This dissertation was also partially supported through national funds provided by Foundation for Science and Technology (FCT) and European Regional Development Fund (ERDF) and COMPETE, under the projects PEst-C/MAR/LA0015/2013, PTDC/MAR-BIO/4694/2014 as well as by the project INNOVMAR – Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR/ INSEAFOOD/ ECOSERVICES), supported by North Portugal Regional i BIOACTIVE SECONDARY METABOLITES FROM THE CULTURE OF THE MARINE SPONGE-ASSOCIATED FUNGUS TALAROMYCES STIPITATUS KUFA 0207 Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Last but not least, I would like to present my greatest gratitude to my family, especially my mother and my brother, for their encouragement and patience. I also thank my friends for their advices and contribution which are very important to my successes. Author’s Declaration I hereby declared that the following original article/ communication were prepared in the scope of this thesis. Scientific Communication 1. Jidapa Noinart, Tida Dethoup, Luís Gales, José Pereira, Ralph Urbatzka, Sara Freitas, Vitor Vasconcelos, Anake Kijjoa. Anti-obesity Activity of Anthraquinones and Other Constituents of the Marine-Derived Fungus Talaromyces stipitatus KUFA 0207. Poster Presentation in the 2nd International Conference of Marine Fungal Natural Products (MaFNaP_2017), 27 -29 June 2017, in Kiel, Germany. Publication 1. Noinart, J.; Buttachon, S.; Dethoup, T.; Gales, L.; Pereira, J.A.; Urbatzka, R.; Freitas, S.; Lee, M.; Silva, A.M.S.; Pinto, M.M.M.; Vasconcelos, V.; Kijjoa, A. A New Ergosterol Analog, a New Bis-Anthraquinone and Anti-Obesity Activity of Anthraquinones from the Marine Sponge-Associated Fungus Talaromyces stipitatus KUFA 0207. Mar. Drugs 2017, 15, 139. doi:10.3390/md15050139 ii BIOACTIVE SECONDARY METABOLITES FROM THE CULTURE OF THE MARINE SPONGE-ASSOCIATED FUNGUS TALAROMYCES STIPITATUS KUFA 0207 Contents Acknowledgement .............................................................................................................. i AutHor’s Declaration .......................................................................................................... ii Figure Index ...................................................................................................................... vii Table Index ......................................................................................................................... xi Abstract ............................................................................................................................. xii Resumo ............................................................................................................................ xiii Abbreviation list .............................................................................................................. xiv CHAPTER 1 ........................................................................................................................ 1 1. General Introduction ..................................................................................................... 2 1.1. Milestone of Natural Products ................................................................................... 2 1.2. The Marine Environments and Bioactive Natural Products ...................................... 3 1.2.1. Relationship between Marine Environments and Bioactive Natural Products ... 3 1.2.2. Importance of Marine Natural Products ............................................................. 4 1.3. Fungi as a Source of Bioactive Secondary Metabolites ........................................... 7 1.3.1. Fungi and Marine Ecology ................................................................................. 8 1.3.2. Sponge - Associated Fungi as a Source of Bioactive Compounds .................... 9 1.4. The Genus Talaromyces ........................................................................................ 12 1.4.1. Taxonomy ........................................................................................................ 12 1.4.1.1. Section Talaromyces ................................................................................ 12 1.4.1.2. Section Emersonii ..................................................................................... 13 1.4.1.3. Section Thermophila ................................................................................. 14 1.4.1.4 Section Purpurea ....................................................................................... 15 1.4.2. The Importance of Talaromyces ...................................................................... 16 1.4.2.1. Importance in Agricultural Applications .................................................... 16 1.4.2.2. Importance in Biotechnological Applications ............................................ 17 1.4.2.3. Importance in Medical Applications .......................................................... 19 1.5. Obesity .................................................................................................................... 20 1.6. Objectives ............................................................................................................... 22 iii BIOACTIVE SECONDARY METABOLITES FROM THE CULTURE OF THE MARINE SPONGE-ASSOCIATED FUNGUS TALAROMYCES STIPITATUS KUFA 0207 CHAPTER 2 ...................................................................................................................... 23 2. Secondary Metabolites from tHe Fungi of tHe Genus Talaromyces Section Talaromyces and Their Bioactivities ............................................................................................................... 24 2.1. Talaromyces flavus ................................................................................................. 26 2.2. Talaromyces helicus ............................................................................................... 31 2.3. Talaromyces luteus ................................................................................................. 32 2.4. Talaromyces stipitatus ............................................................................................ 32 2.5. Talaromyces trachyspermus ................................................................................... 35 2.6. Talaromyces wortmannii ......................................................................................... 36 CHAPTER 3 ...................................................................................................................... 42 3. Materials and MetHods ................................................................................................ 43 3.1. Materials