Ergoline alkaloids are constituents of Clavicipitaceous fungi living on Poaceae plants. Ergoline alkaloids as well as volatile oil are also present in Ipomoea asarifolia Roem. & Schult (Convolvulaceae). Treatment of this plant with two fungicides (Folicur, Pronto Plus) eliminates the ergoline alkaloids but not the volatile oil. Elimination of ergoline alkaloids occurs concomitantly with loss of fungal hyphae associated with secretory glands on the upper leaf surface of the Ipomoea plant. Our observations suggest that accumulation of ergoline alkaloids in the Convolvulaceae may depend on the presence of a plant-associated fungus.
Salutaridinol 7-O-acetyltransferase (EC 2.3.1.150) catalyzes the conversion of the phenanthrene alkaloid salutaridinol to salutaridinol-7-O-acetate, the immediate precursor of thebaine along the morphine biosynthetic pathway. We have isolated a cDNA clone that corresponds to the internal amino acid sequences of the native enzyme purified from a cell suspension culture of opium poppy Papaver somniferum. The recombinant enzyme acetylated the 7-hydroxyl moiety of salutaridinol in the presence of acetyl-CoA. The apparent K m value for salutaridinol was determined to be 9 M and 54 M for acetyl-CoA. The gene transcript was detected in extracts from Papaver orientale and Papaver bracteatum in addition to P. somniferum. Genomic DNA gel blot analysis indicated that there is likely a single copy of this gene in the P. somniferum genome. The amino acid sequence of salutaridinol 7-O-acetyltransferase is most similar (37% identity) to that of deacetylvindoline acetyltransferase of Catharanthus roseus. Salutaridinol 7-O-acetyltransferase is the second enzyme specific to morphine biosynthesis for which we have isolated a cDNA. Taken together with the other cDNAs cloned encoding norcoclaurine 6-O-methyltransferase, (S)-N-methylcoclaurine 3-hydroxylase, the cytochrome P-450 reductase, and codeinone reductase, significant progress has been made toward accumulating genes of this pathway to enable the end goal of a biotechnological production of morphinan alkaloids.
Melleolides and related fungal sesquiterpenoid aryl esters are antimicrobial and cytotoxic natural products derived from cultures of the Homobasidiomycetes genus Armillaria. The initial step in the biosynthesis of all melleolides involves cyclization of the universal sesquiterpene precursor farnesyl diphosphate to produce protoilludene, a reaction catalyzed by protoilludene synthase. We achieved the partial purification of protoilludene synthase from a mycelial culture of Armillaria gallica and found that 6-protoilludene was its exclusive reaction product. Therefore, a further isomerization reaction is necessary to convert the 6–7 double bond into the 7–8 double bond found in melleolides. We expressed an A. gallica protoilludene synthase cDNA in Escherichia coli, and this also led to the exclusive production of 6-protoilludene. Sequence comparison of the isolated sesquiterpene synthase revealed a distant relationship to other fungal terpene synthases. The isolation of the genomic sequence identified the 6-protoilludene synthase to be present as a single copy gene in the genome of A. gallica, possessing an open reading frame interrupted with eight introns.
Purslane extract (PE) is derived from Portulaca oleracea L., a medicinal plant used in traditional medicine for its antidiabetic properties. This randomized, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PE in improving glucose control, blood pressure, and lipid profile in adults with type 2 diabetes mellitus (T2DM) treated with a single oral hypoglycemic agent at baseline. Subjects were randomized to treatment with three capsules of PE/day or a matched placebo. Change from baseline to the week 12 end-of-follow-up visit measures of glucose homeostasis, hemodynamics, and lipid profile was compared by treatment assignment. In addition, these measures were evaluated in a subgroup of "responders," defined as patients whose week 12 HbA1c was lower than baseline values, regardless of treatment assignment. This group was further assessed in subgroups of baseline oral hypoglycemic treatment. A total of 63 participants were treated with either PE (n = 31, 11 females, mean age 52.4 ± 7.9 years) or matched placebo (n = 32, 11 females, mean age 58.3 ± 10.8 years). In the total cohort, systolic blood pressure declined significantly more in the PE group than the placebo group: -7.5 ± 5.0 versus -0.01 ± 0.3 mmHg, P < .0001. In the responders' subgroup, HbA1c declined significantly more in the PE group than the placebo group: -0.8% ± 0.4% versus -0.6% ± 0.5%, P = .03. Few adverse events were reported. These were mild and did not differ by treatment assignment. PE appears to be a safe, adjunct treatment for T2DM, significantly reducing systolic blood pressure in the total cohort and HbA1c in the subgroup of responders.
A novel antibacterial antibiotic, for which the name altersetin is proposed, was isolated from the culture broth of two endophytic Alternaria species. The relative and absolute configuration were assigned by NOESY or CD data, respectively. Altersetin is chemically related to equisetin and showed potent MIC against several pathogenic Gram-positive bacteria, whereas Gram-negative bacteria and pathogenic yeast were not or much less susceptible.Moderate in vivo efficiacy was observed for altersetin in a murine sepsis model.
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