Marine natural products have become an increasingly important source of new drug leads during recent years.In an attempt to identify novel anti-microbial natural products by bioprospecting deep-sea Actinobacteria,thre...Marine natural products have become an increasingly important source of new drug leads during recent years.In an attempt to identify novel anti-microbial natural products by bioprospecting deep-sea Actinobacteria,three new angucyclines,nocardiopsistins A-C,were isolated from Nocardiopsis sp.strain HB-J378.Notably,the supplementation of the rare earth salt Lanthanum chloride(LaCl3)during fermentation of HB-J378 significantly increased the yield of these angucyclines.The structures of nocardiopsistins A-C were identified by 1D and 2D NMR and HR-MS data.Nocardiopsistins A-C have activity against MRSA(methicillin-resistant Staphylococcus aureus)with MICs of 3.12–12.5μg/mL;the potency of nocardiopsistin B is similar to that of the positive control,chloramphenicol.Bioinformatic analysis of the draft genome of HB-J378 identified a set of three core genes in a biosynthetic gene cluster that encode a typical aromatic or type II polyketide synthase(PKS)system,including ketoacyl:ACP synthaseα-subunit(KSα),β-subunit(KSβ)and acyl carrier protein(ACP).The production of nocardiopsistins A-C was abolished when the three genes were knocked out,indicating their indispensable role in the production of nocardiopsistins.展开更多
Natural product mayamycin is the first example in the angucycline class featuring a C-glycoside linkage at the C5-position of the benz[a]anthracenone core with remarkable biological activities. We successfully synthes...Natural product mayamycin is the first example in the angucycline class featuring a C-glycoside linkage at the C5-position of the benz[a]anthracenone core with remarkable biological activities. We successfully synthesized the two retrosynthetic fragments, but found that the final C-glycosylation did not occur. Alternatively, an A-ring satu- rated aglycon was prepared, but the proposed C-glycosylation still did not proceed. Finally, a simplified substrate was used and the subsequent C-glycosylation went through smoothly, giving a two-ring less analogue of mayamy- cin.展开更多
Angucyclines are one of the largest families of aromatic polyketides with various chemical structures and bioactivities.Decades of studies have made it easy for us to depict the picture of their early biosynthetic pat...Angucyclines are one of the largest families of aromatic polyketides with various chemical structures and bioactivities.Decades of studies have made it easy for us to depict the picture of their early biosynthetic pathways.Two families of oxygenases,the FAD-dependent oxygenases and the ring opening oxygenases,contribute to the formation of some unique skeletons of atypical angucyclines.The FAD-dependent oxygenases involved in the biosynthetic gene clusters of typical angucyclines catalyze two hydroxylation reactions at C-12 and C-12b of prejadomycin,while their homolog JadH in jadomycin gene cluster catalyze the C-12 hydroxylation and 4a,12b-dehydration reactions of prejadomycin,which leads to the production of dehydrorabelomycin,a common intermediate during the biosynthesis of atypical angucyclines.Ring opening oxygenases of a unique family of oxygenases catalyze the oxidative CeC bond cleavage reaction of dehydrorabelomycin,followed by different rearrangement reactions,resulting in the formation of the various chemical skeletons of atypical angucyclines.These results suggested that the functional differentiation of these oxygenases could apparently enrich the sources of aromatic polyketides with greater structure diversities.展开更多
Angucyclines are aromatic polyketides produced by typeⅡpolyketide synthase(PKS)exclusively from actinomycetes.These natural products contain hydrolyzable sugar moieties that attach to various positions of the polyket...Angucyclines are aromatic polyketides produced by typeⅡpolyketide synthase(PKS)exclusively from actinomycetes.These natural products contain hydrolyzable sugar moieties that attach to various positions of the polyketide skeleton and expand the structural diversity.We here report the isolation of two new angucyclines(1 and 2)from the deep-sea-derived Streptomyces sp.PKU-MA01297,which was isolated from a sediment sample collected at a depth of 3202 meters from the Indian Ocean.The structures of the two new compounds were elucidated based on comprehensive methods,including NMR,MS and CD analysis.Compounds 1 and 2 featured a 1-O-β-D-glucopyranosyl moiety that has not been reported for angucyclines.Several biological activity assays,including antibacterial,cytotoxicity and anti-inflammatory assays,were carried out,and compounds 1 and 2 showed no activities.These results set the stage for biosynthetic research and more biological activity assays in the future.展开更多
基金This work was supported in part by the NIH grant CA209189.
文摘Marine natural products have become an increasingly important source of new drug leads during recent years.In an attempt to identify novel anti-microbial natural products by bioprospecting deep-sea Actinobacteria,three new angucyclines,nocardiopsistins A-C,were isolated from Nocardiopsis sp.strain HB-J378.Notably,the supplementation of the rare earth salt Lanthanum chloride(LaCl3)during fermentation of HB-J378 significantly increased the yield of these angucyclines.The structures of nocardiopsistins A-C were identified by 1D and 2D NMR and HR-MS data.Nocardiopsistins A-C have activity against MRSA(methicillin-resistant Staphylococcus aureus)with MICs of 3.12–12.5μg/mL;the potency of nocardiopsistin B is similar to that of the positive control,chloramphenicol.Bioinformatic analysis of the draft genome of HB-J378 identified a set of three core genes in a biosynthetic gene cluster that encode a typical aromatic or type II polyketide synthase(PKS)system,including ketoacyl:ACP synthaseα-subunit(KSα),β-subunit(KSβ)and acyl carrier protein(ACP).The production of nocardiopsistins A-C was abolished when the three genes were knocked out,indicating their indispensable role in the production of nocardiopsistins.
文摘Natural product mayamycin is the first example in the angucycline class featuring a C-glycoside linkage at the C5-position of the benz[a]anthracenone core with remarkable biological activities. We successfully synthesized the two retrosynthetic fragments, but found that the final C-glycosylation did not occur. Alternatively, an A-ring satu- rated aglycon was prepared, but the proposed C-glycosylation still did not proceed. Finally, a simplified substrate was used and the subsequent C-glycosylation went through smoothly, giving a two-ring less analogue of mayamy- cin.
基金National Natural Science Foundation of China(Grants:31670800,31470176,and 31130001)Ministry of Science and Technology of China(Grants:2014CB910400).
文摘Angucyclines are one of the largest families of aromatic polyketides with various chemical structures and bioactivities.Decades of studies have made it easy for us to depict the picture of their early biosynthetic pathways.Two families of oxygenases,the FAD-dependent oxygenases and the ring opening oxygenases,contribute to the formation of some unique skeletons of atypical angucyclines.The FAD-dependent oxygenases involved in the biosynthetic gene clusters of typical angucyclines catalyze two hydroxylation reactions at C-12 and C-12b of prejadomycin,while their homolog JadH in jadomycin gene cluster catalyze the C-12 hydroxylation and 4a,12b-dehydration reactions of prejadomycin,which leads to the production of dehydrorabelomycin,a common intermediate during the biosynthesis of atypical angucyclines.Ring opening oxygenases of a unique family of oxygenases catalyze the oxidative CeC bond cleavage reaction of dehydrorabelomycin,followed by different rearrangement reactions,resulting in the formation of the various chemical skeletons of atypical angucyclines.These results suggested that the functional differentiation of these oxygenases could apparently enrich the sources of aromatic polyketides with greater structure diversities.
基金National Natural Science Foundation of China(Grant No.81741148,81573326,81673332,21877002)COMRA Project of China(Grant No.DY135-B2-08)China Postdoctoral Science Foundation(Grant No.2018M641123)
文摘Angucyclines are aromatic polyketides produced by typeⅡpolyketide synthase(PKS)exclusively from actinomycetes.These natural products contain hydrolyzable sugar moieties that attach to various positions of the polyketide skeleton and expand the structural diversity.We here report the isolation of two new angucyclines(1 and 2)from the deep-sea-derived Streptomyces sp.PKU-MA01297,which was isolated from a sediment sample collected at a depth of 3202 meters from the Indian Ocean.The structures of the two new compounds were elucidated based on comprehensive methods,including NMR,MS and CD analysis.Compounds 1 and 2 featured a 1-O-β-D-glucopyranosyl moiety that has not been reported for angucyclines.Several biological activity assays,including antibacterial,cytotoxicity and anti-inflammatory assays,were carried out,and compounds 1 and 2 showed no activities.These results set the stage for biosynthetic research and more biological activity assays in the future.
