Studies On Co-cultivation Of Aspergillus Flavipes And Chaetomium Globosum,and Secondary Metabolites Of Two Other Fungi

Four chapters were included in the dissertation.In the first chapter,the secondary metabolites from the co-culture of Aspergillus flavipes and Chaetomium globosum,were systematic studied.The plausible biogenetic pathways of the cytochalasans with thiazine ring were discussed.The second chapter was about the secondary metabolites and their bioactivities from Metarhizium anisopliae.The thired chapter was about the research of Talaromyces purpurogenus.The last chapter is a review of a glossary of approaches for inducing,activating and upregulating the biosynthesis of microorganic cryptic or silent natural products.Cytochalasans are composed of polyketides and amino acids and are well known for having a wide variety of biological activities,such as cytotoxic,antifouling,nematicidal,and anti-inflammatory properties.To date,over 300 cytochalasans with versatile structures and diverse bioactivities have been isolated and characterized.In our previous studies on this class of compounds,a series of bioactive cytochalasans with novel skeletons were isolated from Aspergillus flavipes and Chaetomium globosum;armochaeglobine A and asperchalasine A are representatives of these compounds.These results in conjunction with literature data demonstrated that these two fungi are rich sources of cytochalasans,and they produce these compounds in a reliable manner.However,many biosynthetic genes of fungi remain silent or less active in laboratory cultivations,in order to get more structurally novel cytochalasans,we applied co-culture methodology to A.flavipes and C.globosum to determine if there are silent genes that could be activated.The isolation of cocultivation yielded 80 compounds(39 new structures),including three new skeletons with a thiazine moiety;one cytochalasan with an uniquely degraded indole ring;six chaetoglobosin-type cytochalasans with oxygenated C-10;five aspochalasin-type cytochalasans possessing hydroxylated Me-12;and six furano-polyenes.The selected compounds were tested for their cytotoxic,immunomodulatory and antibacterial activities,and some of them showed significant activities against cancer cell lines.The secondary metabolites of Metarhizium anisopliae,collected from the mangrove of Xiamen,Fujian province,was systematically investigated.Eleven compounds including seven new structures were isolated and characterizated from the rice solid cultures of Metarhizium anisopliae.The selected compounds were tested for their cytotoxic and anti-inflammatory properties,and metarhizoside A and B exhibited moderate activities against LPS-stimulated RAW264.7 cells.The secondary metabolites of Talaromyces purpurogenus,isolated from a mud sample collected on the coastal beach in Qinghuangdao County,Hebei Province,China,was systematically investigated.Six compounds including two new structures were isolated and characterizated from the rice solid cultures of Penicillium purpurogenum.9,10-diolhinokiic acid(1)is the first thujopsene-type sesquiterpenoid containing a 9,10-diol moiety,and roussoellol C(2)possesses a novel tetracyclic fusicoccane framework with an unexpected hydroxyl at C-4.Compounds 1-3 exhibited cytotoxicities against five human cancer cell lines including SW480,HL-60,A549,MCF-7,and SMMC-7721The systematically investigations of cocultivation resulted in the isolation of a class of more functionalized cytochalasans,which greatly enriched the structural diversity of cytochalasans.This study also illustrates that co-cultivation is an effective method for obtaining structurally diverse and biologically interesting cytochalasans.