ABSTRACT
Laggera pterodonta, known in China as 'Choulingdan' for its stimulous odor, has long been used as traditional herbal medicine. The essential oil of L. pterodonta, which exhibits various pharmacological activities, is a rich resource of monoterpenes and sesquiterpenes. To date, however, the terpene synthases responsible for their production remain unknown. In present study, a new terpene synthase gene (LpNES1) was identified from L. pterodonta, transcript level of which was significantly upregulated in response to methyl jasmonate treatment. Recombinant LpNES1 could synthesize (E)-nerolidol and minor ß-farnesene from farnesyl diphosphate and linalool from geranyl diphosphate in vitro. Whereas, only sesquiterpenes including (E)-nerolidol and minor ß-farnesene were released when LpNES1 was reconstituted in yeast, even coexpressed with a geranyl diphosphate synthase (ERG20WW). Combined with subcellular localization experiment, the result indicated that the cytosol-targeted LpNES1 was responsible for (E)-nerolidol biosynthesis exclusively in L. pterodonta. Additionally, the expression level of LpNES1 gene was more prominent in floral buds than that in other tissues. LpNES1 characterized in present study not only lays the molecular foundation for sesquiterpene biosynthesis of L. pterodonta, but provides a key element for further biosynthesis of bioactive compound in microbes.
Subject(s)
Alkyl and Aryl Transferases/genetics , Alkyl and Aryl Transferases/metabolism , Asteraceae/enzymology , Asteraceae/genetics , Plants, Medicinal , Acetates/pharmacology , Asteraceae/metabolism , Cyclopentanes/pharmacology , Genes, Plant , Oxylipins/pharmacology , Phytochemicals/biosynthesis , Sesquiterpenes/metabolism , Up-RegulationABSTRACT
Forskolin is a complex labdane plant diterpenoid, which has been used in the treatment of a variety of diseases based on its activity as an activator of adenosine monophosphate(cAMP) cyclase. Natural forskolin exists only in the cork layer of the root of Coleus forskohlii. Due to the complexity of the extraction and chemical synthesis processes, the yield and purity of forskolin cannot meet commercial requirements. In recent years, with the rapid development of synthetic biology and the analysis and interpretation of many diterpene biosynthetic pathways, a new approach has been provided for the green production of forskolin. In this paper, the structure, activity, biosynthetic pathway and the heterologous biosynthesis of forskolin were reviewed. The problems and solutions in the heterologous biosynthesis of forskolin were also discussed and summarized, which will provide references for the construction of high-yielding forskolin engineering strains.
Subject(s)
Biosynthetic Pathways , ColforsinABSTRACT
5rolGLP-HV is a promising dual-function peptide for the treatment of diabetes and thrombosis simultaneously. For investigating the therapeutic mechanism of 5rolGLP-HV for type 2 diabetes mellitus (T2DM), STZ-induced diabetic mice were established and treated with 5rolGLP-HV. The results showed that daily water and food intake, blood glucose, serum and pancreatic insulin levels significantly decreased after 5rolGLP-HV treatment with various oral concentrations, and 16 mg/kg was the optimal dose for controlling diabetes. 5rolGLP-HV treatment decreased the MDA levels and the T-SOD activity in serum and pancreatic of diabetic mice (but not up to significant difference), and significantly increased the expression of signal pathways related genes of rolGLP-1, also the density of insulin expression and the numbers of apoptosis cells in islets of diabetic mice were significantly decreased in comparison to the negative diabetic mice. These effects above may be clarified the hypoglycemic mechanisms of 5rolGLP-HV, and 5rolGLP-HV may be as a potential drug for diabetes in future.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Glucagon-Like Peptide 1/pharmacology , Hypoglycemic Agents/pharmacology , Insulin/blood , Recombinant Proteins/pharmacology , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Cyclic AMP-Dependent Protein Kinases/genetics , Cyclic AMP-Dependent Protein Kinases/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Drinking/drug effects , Drug Evaluation, Preclinical , Eating/drug effects , Gene Expression Regulation , Glucagon-Like Peptide 1/biosynthesis , Glucagon-Like Peptide-1 Receptor/genetics , Glucagon-Like Peptide-1 Receptor/metabolism , Hirudins/chemistry , Hypoglycemic Agents/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , MAP Kinase Kinase Kinases/genetics , MAP Kinase Kinase Kinases/metabolism , Male , Malondialdehyde/antagonists & inhibitors , Malondialdehyde/metabolism , Mice , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Recombinant Proteins/biosynthesis , Streptozocin , Superoxide Dismutase/metabolismABSTRACT
Santalene and santalol are the main components of valuable perfume sandalwood essential oil, and have good antibacterial, anti-oxidation and anti-tumor activities. Commercial sandalwood essential oil is mainly extracted from sandalwood tree that grows slowly and is difficult to cultivate. In addition, the extraction recovery of sandalwood essential oil from sandalwood tree is too low to meet the market demand. These factors make sandalwood essential oil expensive. An option is to use genetic engineering and molecular biological methods to heterologously express related synthase of santalene and santalol in microbial host. In this paper, the biosynthesis progress of santalene and santalol synthase, as well as the optimization of mevalonate metabolic pathways in the hosts are summarized. Furthermore, the strategies of applying protein engineering technology to carry out orthomutation of santalene synthase were also discussed, to provide reference for the optimal biosynthesis of santalene and santalol.
Subject(s)
Plant Oils/chemistry , Santalum/chemistry , Sesquiterpenes/metabolism , Industrial Microbiology , Metabolic Networks and Pathways , Mevalonic Acid/metabolism , Polycyclic Sesquiterpenes , Protein EngineeringABSTRACT
A new phenylspirodrimane dimer, named stachartarin A (1), was isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum. Its structures were elucidated by means of spectroscopic methods. At the same time, the compound was tested for its cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells.