Function And Mechanism Exploring Of Marine Microorganisms And Their Natural Products In Prevetion And Treatment Of Two Hepatoma Carcinogenic Factors

The marine system is the largest ecosystem of the earth,it contains large amounts of microorganism.As the special living environments of these microorganisms,some new metabolism types are included.Many natural products of the microorganisms have been developed as prodrugs,and this provides good resources for screening of new active products.Meanwhile,it also offers various resources for development of industrial bacteria.In this study,diversity of marine microorganisms and their natural products were exploited to screen inhibitors of hepatitis C virus,and to screen remediation microorganisms of heavy metal pollution.Their primary action mechanisms were also explored.Hepatitis C virus(HCV)is the major etiological agent of non-A and non-B hepatitis,and its therapeutic options are still limited.Here we established two high throughput screening systems focusing on the interactions between HCV and host factors,and screened HCV inhibitors from natural products of marine microorganisms.One of the screening system was based on the interaction between HCV IRES and human e IF3,and fluorescence polarization(FP)method was adopted;the other system was based on interaction of HCV NS5 A and human CypA proteins,while fluorescence resonance energy transfer(FRET)technology was used.From the screening systems,two active agents(Mucl39526 and NP39)were found to interrupt the IRES-e IF3 interaction,which inhibit both IRES-dependent and Cap-dependent translation;another active agent HP-3 was shown to promote the IRES-eIF3 interaction,and it could promote IRES-dependent translation specifically.Also the mechanisms of the three active agents were tentatively explored.Heavy metal pollution is another important etiological agent of hepatocellular carcinoma,and microbial remediation is a promising technology for treatment of heavy metal pollution.Here we based on the fact that calcite precipitation bacteria could coprecipitate heavy metal irons,and the calcite precipitation bacteria are always associated with urea degradation,calcite precipitation bacteria Brevibacterium lines 258 was screened out from marine sediment.Technologies of SEM-EDX,TEM-SAED,XRD and FTIR were adopted to study the precipitation and coprecipitation of B.lines 258,and an inductively coupled plasma source mass spectrometer was used to measure concentrations of dissolved metal irons to count the metal irons’ removal rates of B.lines 258 strain.The results showed that B.lines 258 could effectively coprecipitate heavy metal irons of Cu2+,Zn2+,Mn2+ and Sr2+.Also the whole genome and transcriptome of B.lines 258 were sequenced,and genes related to urea degradation,calcite precipitation and heavy metal resistance were found,and ABC transporters were closely related with bioremediation of B.lines 258.The B.lines 258 was shown to be a promising industrial strain for heavy metal remediation.