Biologically Active Natural Products From Marine Microorganisms

The marine environment demonstrates a particular focus on exploring new sources of bioactive natural products from the remarkable diversity of microorganisms.Therefore,the most suitable target for the discovery of novel secondary metabolites is to deceive the problem of resistant pathogens.In addition,marine fungi and bacteria are among the most skilled clumps/masses or clusters of secondary metabolite producers and are important for drug discovery programs.However,only a portion of the genes in the production of chemical compounds by living organisms are transcribed under conventional in vitro conditions involving the culture of axenic/sterile microbial strains.In other respects,many biosynthetic genes remain inactive and are not expressed under laboratory conditions,so that the chemical diversity of the microbial compounds obtained through fermentation is very limited.Thus,various stress techniques activated latent or potential gene clusters that resulted in the separation of potential metabolites.This study focused on the analysis of two new angucycline antibiotics by using the "Metal Stress Technique" applied in the discovery of stremycin A(1)and B(2),in addition to four known compounds(3-4),which were isolated from the culture filtrate of a marine Streptomyces pratensis NA-ZhouSl.New cryptic antibiotics 1-2 were further identified based on spectroscopic techniques such as HR-TOF-MS,ESI-MS/MS,ID,and 2D NMR experiments.In addition,untreated and cobalt treated cultures(800 ?M)have successfully isolated six known compounds,namely,ergosterol(7),diorcinol(8),(+)-curcutetraol(9),cyclopenol(10),7-methoxycyclopenin(11),and the cottoquinazoline A(12)from the strain XZ-2.This strain is a collection of marine hydrothermal vent Aspergillus sp.isolated from the gland of hydrothermal crab Xenograpsus testudinatus.Stremycin A(1)and B(2)exhibited antimicrobial activities against P.seudomonas aeruginosa,MRSA,Klebsiella pneumonia,and Escherichia coli with equal MIC values of 16 ?g/mL,while these antibiotics showed inhibition against Bacillus subtilis at MIC value of around 8-16 ?g/mL,respectively.The known compounds 7-methoxycyclopenin 11 showed activity against Escherichia coli at MIC values around 32?g/mL while cyclopenol 10 showed no activity.The diorcinol 8 exhibited the inhibitory activity against Staphylococcus aureus and Bacillus subtilis at MIC values around 16-32 ?g/mL,respectivelySimilarly,a novel indene derivative,methyl 2-(4-hydroxybenzyl)-1,7-dihydroxy-6-(3-methylbut-2-enyl)-1H-indene-l-carboxylate(13)and known metabolites(14-24)were purified from the ethyl acetate extract of the plant-associated fungus Aspergillus flavipes Y-62,isolated from the stems of Suaeda glauca(Bunge)Bunge which was collected along Zhoushan coast,Zhejiang province,East China.The structure of a new indene derivative was elucidated by extensive use of spectroscopic techniques like 1D,2D NMR,and HR-TOF-MS.Among the tested compounds,the structure of 13 showed weaker activity in comparison to the positive control tetracycline against methicillin-resistant S.aureus(MRSA)with the MIC value of 128 ?g/mL,and against K.pneumoniae and P.aeruginosa with equal MIC values of 32 ?g/mL,respectively.Further,nine known compounds including cyclic tetrapeptide,diketopiperazines and alkaloid were obtained from the ethyl acetate layer of actinomycetes sp.NB-ZhouS2,which were collected from the marine sediments along Zhoushan coast,Zhejiang province,East China.These chemical structures(25-33)are consistent with 1D(1H,13C)NMR experiments and are associated with earlier studies published in literature,i.e,cyclo-[Leucyl-prolyl]2(25),N-acetyltyramine(26),cyclo-(L-Pro-L-Val)(27),cyclo-(R-Pro-R-Leu)(28),3-hydroxyacetylindole(29),cyclo-(4-methyl-R-Pro-S-Nva)(30),cyclo-(L-Pro-L-Phe)(31),cyclo-(L-Pro-L-Tyr)(32)and 4-methyl-5,6-dihydro-2H-pyran-2-one(33).