Discovery Of Novel Secondary Metabolites In Two Fungi

Fungi,as a large biological group in the biosphere,are abundant and diverse in secondary metabolites,which is an important resource for the research and development of medicine and agriculture.Fungi come from a variety of sources,such as soil,water,plants,animals,and so on.Coprophilous fungi are a kind of microbial community that co-exists with animals.It maintains its growth by absorbing rich nutrients from animal feces.As a fungus growing in a special habitat,the secondary metabolites have to be significantly different from other fungal groups.In order to explore the biological and ecological functions of this kind of fungi,we studied the chemical properties of Amphichorda guana LC5815,a fungus from bat droppings,in order to find out the secondary metabolites with novel structure and remarkable biological activity.The secondary metabolites of Amphichorda guana LC5815 solid fermentation were separated by silica gel and gel column chromatography,and high pressure preparation chromatography.The compounds were identified by NMR,MS,UV and IR,and five compounds were isolated and identified as oxirapentyns L to N(1 to 3),oxirapentyn B(4)and iso-isariin B(5),in which compounds 1 to 3 were new compounds.With the decrease of research objects,it is more and more difficult and time-consuming to find new novel compounds by traditional research methods.Therefore,it is urgent to find new strategies to improve the probability of finding new compounds.At present,novel compounds in fungi are discovered by genetic manipulation,including epigenetic regulation,heterologous expression and gene knockout.A series of novel structural compounds were isolated from 4 gene knockout mutants in our previous study.Based on the mature genetic system of the study group,we knock out some genes of the Trichoderma hypoxylon and obtained a mutant strain TYHL 33,which did not produce trichothecenes and epipolythiodiketopiperazines.The mutants were studied chemically,combined with various separation techniques and chromatographic techniques,and 16 compounds were obtained from its ethyl acetate extract: tricholactione A(TH-1),tricholactione B(TH-2)tichodermacid(TH-3),4-hydroxyphenethyl alcohol(TH-4),4-hydroxyphenylacetic acid(TH-5),2-hydroxyphenylacetic acid(TH-6),methyl 4-hydroxyphenylacetate(TH-7),3,4-dihydroxyphenylethanol(TH-8),hydroheptelidic acid(TH-9),3-indoleacetic acid(TH-10),3,4-dihydroxyphenylacetic acid(TH-11),ferulic acid(TH-12),methyl 3-indole-acetic acid(TH-13),1-acetyl-?-carboline(TH-14),monaspilosin(TH-15),and phenylacetic acid(TH-16),in which compounds TH-1 to TH-3 are new compounds.Three new compounds TH-1 to TH-3 were found through gene knockout of Trichoderma hypoxylon.The results show that gene knockout is a strategy to improve the probability of finding new compounds.