Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa T...Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa TPS1 generated a 5/8/6/5 tetracyclic sesteraltererol(1)and its absolute stereochemistry was determined by X-ray crystallographic analysis of its derivative 10,11-epoxysesteraltererol(2),which enabled revision of the absolute configuration of C7 of sesterfisherol produced by Nf SS and PTTS014 characterized previously and its derivative 10,11-epoxysesterfisherol.Aa TPS2 produced a 5/15 bicyclic preterpestacin I(3).Site-directed mutagenesis suggested that F192 in Aa TPS1 was likely involved in controlling of the hydroxylation of C12,and eight amino acids were important for the enzyme activity of Aa TPS1 and Aa TPS2.The engineered Escherichia coli and Saccharomyces cerevisiae strains were constructed for the productions of compounds 1 and 3,and the highest titer of compound 1 reached 62.3 mg/L in shake-flask culture.Both compounds 1 and 2 showed anti-adipogenic activity.展开更多
Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactiviti...Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactivities deserve extensive exploration.RNA-seq analysis indicated that leucosceptroid B,a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum,significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans.Furthermore,leucosceptroid B was found to reduce fat storage,and downregulate the expression of two stearoyl-CoA desaturase(SCD)genes fat-6 and fat-7,and a fatty acid elongase gene elo-2 in wild-type C.elegans.In addition,leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6;fat-7 double mutant.These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6,fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid.These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.展开更多
Three new drimane sesquiterpenoids(1–3)together with the known 2a-hydroxyisodrimeninol(4),and a new isochromone derivative(5),were obtained from the solid cultures of fungal strain Pestalotiopsis sp.M-23,an endophyti...Three new drimane sesquiterpenoids(1–3)together with the known 2a-hydroxyisodrimeninol(4),and a new isochromone derivative(5),were obtained from the solid cultures of fungal strain Pestalotiopsis sp.M-23,an endophytic fungus isolated from the leaves of Leucosceptrum canum(Labiatae).Their structures were determined by comprehensive 1D and 2D NMR,and MS analyses.The metabolites were evaluated for their antibacterial activities,and compound 3 showed weak inhibitory activity against Bacillus subtilis.展开更多
基金supported financially by the National Natural Science Foundation of China(Nos.21937006 and 22107103)the Yunnan Key Research and Development Program(No.2019ZF011–2)the“Western Light”Program of the CAS(to Y.Liu)。
文摘Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa TPS1 generated a 5/8/6/5 tetracyclic sesteraltererol(1)and its absolute stereochemistry was determined by X-ray crystallographic analysis of its derivative 10,11-epoxysesteraltererol(2),which enabled revision of the absolute configuration of C7 of sesterfisherol produced by Nf SS and PTTS014 characterized previously and its derivative 10,11-epoxysesterfisherol.Aa TPS2 produced a 5/15 bicyclic preterpestacin I(3).Site-directed mutagenesis suggested that F192 in Aa TPS1 was likely involved in controlling of the hydroxylation of C12,and eight amino acids were important for the enzyme activity of Aa TPS1 and Aa TPS2.The engineered Escherichia coli and Saccharomyces cerevisiae strains were constructed for the productions of compounds 1 and 3,and the highest titer of compound 1 reached 62.3 mg/L in shake-flask culture.Both compounds 1 and 2 showed anti-adipogenic activity.
基金supported by the National Science Fund for Distinguished Young Scholars(No.31525005)National Natural Science Foundation of China(Nos.21937006,31770390 and 31800298)+3 种基金Yunnan Key Research and Development Program(No.2019ZF011-2)Yunnan Innovative Research Team for Discovery and Biosynthesis of Bioactive Natural Products(No.2018HC012)Science Foundation of Yunnan(No.2018FA017)Youth Innovation Promotion Association and “Western Light” Program of CAS(awarded to LIU Yan)
文摘Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactivities deserve extensive exploration.RNA-seq analysis indicated that leucosceptroid B,a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum,significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans.Furthermore,leucosceptroid B was found to reduce fat storage,and downregulate the expression of two stearoyl-CoA desaturase(SCD)genes fat-6 and fat-7,and a fatty acid elongase gene elo-2 in wild-type C.elegans.In addition,leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6;fat-7 double mutant.These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6,fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid.These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.
基金This work was supported financially by the National Natural Science Foundation of China(Nos.31525005,U1202263,31570362)the Youth Innovation Promotion association of Chinese Academy of Sciences(awarded to Shi-Hong Luo)+1 种基金the“Western Light”Program of Chinese Academy of Sciences(awarded to Shi-Hong Luo)the“Hundred Talents Program”of the Chinese Academy of Sciences(awarded to Sheng-Hong Li).
文摘Three new drimane sesquiterpenoids(1–3)together with the known 2a-hydroxyisodrimeninol(4),and a new isochromone derivative(5),were obtained from the solid cultures of fungal strain Pestalotiopsis sp.M-23,an endophytic fungus isolated from the leaves of Leucosceptrum canum(Labiatae).Their structures were determined by comprehensive 1D and 2D NMR,and MS analyses.The metabolites were evaluated for their antibacterial activities,and compound 3 showed weak inhibitory activity against Bacillus subtilis.
