Bioactive natural products are the material bases of Chinese materia medica resources. With successful applications of synthetic biology strategies to the researches and productions of taxol, artemisinin and tanshinone, etc, the potential ability of synthetic biology in the sustainable utilization of Chinese materia medica resources has been attracted by many researchers. This paper reviews the development of synthetic biology, the opportunities of sustainable utilization of Chinese materia medica resources, and the progress of synthetic biology applied to the researches of bioactive natural products. Furthermore, this paper also analyzes how to apply synthetic biology to sustainable utilization of Chinese materia medica resources and what the crucial factors are. Production of bioactive natural products with synthetic biology strategies will become a significant approach for the sustainable utilization of Chinese materia medica resources.

Diterpenes, an important class of natural compounds, are widely distributed in nature. As the valuable diterpenoids continue to be found, diterpene synthase in the course of diterpene synthesis get as much attention as possible. The multiformity of end-product-diterpenoids were also due to the diversity of diterpene synthase. This paper focuses on the advances in recent biosynthesis pathway of diterpene and types, cloning, catalytic mechanism, synthetic biology application.

OBJECTIVE:To explore the construction effect of rational drug use monitoring system on the improvement of clini-cal drug use in the hospital. METHODS:The data about the construction of rational drug use monitoring system were collected from our hospital,including pharmacist workstation prescription check(check before prescription/medical order charging to realize warning in advance),clinical pharmacy management system prescription comment(realize prescription/medical order comment after-wards)and adverse drug reaction/adverse drug event(ADR)reporting information platform(realize online ADR reporting)during 2014-2015. The data was analyzed to evaluate the effectiveness of system construction. RESULTS & CONCLUSIONS:There were a total of 3 417 329 prescriptions audited by the pharmacist workstation within 2 years through improving system functions,includ-ing 7 315 prescriptions were returned to doctors to be modified,the percentage of which declined from 0.39% to 0.08%. The pass rate of prescription comment pre-judgment increased from 81.2% to 90.4% in 2015 by clinical pharmacy management system. The valid case number of ADR monitoring and reporting increased from 186 cases to 267 cases,involving all department of our hospi-tal. The construction of rational drug use monitoring system in our hospital can improve the standardization of prescription/medical orders,the level of rational drug use and the case number of ADR,which has achieved the expected results.

This study reported the obtainment of the full-length cDNA of Salvia miltiorrhiza hairy roots (Abbr: SmHDR, GenBank number: JX233817), via extracting Salvia miltiorrhiza hairy roots total RNA, designing specific primers according to the transcriptome data and using the RACE strategy, and then analyzed it with bioinformatics approaches. On this basis, using the real-time PCR to detect SmHDR gene expression after Ag+ induction, and testing tanshinones contents of corresponding samples by UPLC. SmHDR has 1 647 nucleotides, and an open reading frame (ORF) encoding a protein of 463 amino acid residues. The deduced protein has isoelectric point (pI) of 5.72 and a calculated molecular weight about 51.88 kD. In the secondary structure, the percentage of alpha helix, beta turn and random coil were 35.64%, 20.30% and 44.06%, respectively. Sequence alignment and phylogenetic analysis demonstrated that SmHDR had relative close relationship to the HDR of Picrorhiza kurrooa, similar to HDR from other species of plants. Real time PCR results indicated that elicitor of Ag+ stimulated the increase of mRNA expression of SmHDR. At the same time, results of ultra performance liquid chromatography (UPLC), used to examine the accumulation of diterpenoid tanshinones in hairy roots, showed that the contents of diterpenoid tanshinones in hairy roots of Salvia miltiorrhiza were increased dramatically at 12 h after treated with Ag+, and then decreased significantly. This result showed a positive correlation between the levels of mRNA expression and tanshinones accumulation in Salvia miltiorrhiza stimulated by Ag+. The content of tanshinones was gradually raised, and it had an obvious increase at 120 h. The bioinformatics analysis and gene expression indicated that SmHDR might be involved in tanshinones biosynthesis, which laid the foundation for further study of secondary metabolic regulation mechanism of tanshinones.

This paper introduced a new method of "ingredient difference phonetypical cloning" for functional gene clone of medicinal plants, which might solve the difficulties in isolating genes encoding enzymes for the biosynthesis of secondary metabolites by usual ways. Concepts, mechanisms and methods were systematically introduced and possibility was proved by experiments. The method showed the extra superiority of for the isolation of the genes belonged to unknown metabolic pathway and little information about its sequences. The method provides a new way to isolate functional gene cloning from Chinese herbs and a fundament for the further study on medicinal plant genetic engineering.
Cloning, Molecular ; Drugs, Chinese Herbal ; metabolism ; Genes, Plant ; genetics ; Genetic Engineering ; methods ; Phenotype ; Plants, Medicinal ; genetics ; metabolism ; Reproducibility of Results ; Time Factors

Numerical taxonomic studies were carried out in order to elucidate the taxonomic relationship among 17 species belonging to Paris. Eighteen characters including 10 morphological, 4 pollen morphological, 2 cytotalonomical and 2 habitat characters were used for the analysis. On basis of UPGMA clustering analysis, two subgenus and seven groups were recognized. The classification of the two subgenus was different from the opinion of subgenus Daiswa and subgenus Paris by Li Heng. The classification of sect. Dunnianae, sect. Axiparis and sect. Paris was correspondence with the classification of Li Heng. But sect. Fargesianae, sect. Marmoratae and sect. Thibeticae which were established based on the especially characters by Li Heng were put into cluster 2, cluster 3 and cluster 4.
Magnoliopsida ; anatomy & histology ; classification ; Phylogeny

OBJECTIVETo study the mechanism of secondary metabolites of some phenolic acids in the hairy roots of Salvia miltiorrhiza induced by methyl jasmonate.

METHODThe hairy roots of S. miltiorrhiza were induced with methyl jasmonate (100 micromol x L(-1)) and collected at 0, 12, 24, 36 h after treatment. Real-time quantitative PCR was used for detecting the mRNA expression level of the key enzyme genes on the secondary metabolites pathway of rosmarinic acid, while a LC-MS method was developed to determine the content of rosmarinic acid, caffeic acid and salvianolic acid B.

RESULT AND CONCLUSIONThe concentration of phenolic acids grew up and accumulated quickly in the hairy roots with exogenous signal molecule MJ induced, and it was showed that the content of CA and RA reached the maximum after 24 h and the content of LAB reached the maximum in 36 h by MJ induced. The induction mechanism may be activated with different levels of RA synthesis in PAL, 4CL, C4H genes on the key enzyme phenylalanine pathway and TAT, HPPR genes on tyrosine pathway. The time of gene expression was different, among them, 4CL and PAL genes were more important. In a word, the result can provide some basis data about the mechanism of secondary metabolites of phenolic acids for further research.

Cyclopentanes ; analysis ; metabolism ; Gene Expression Regulation, Plant ; Hydroxybenzoates ; analysis ; metabolism ; Oxylipins ; analysis ; metabolism ; Plant Proteins ; genetics ; metabolism ; Plant Roots ; chemistry ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; enzymology ; genetics ; metabolism

OBJECTIVETo establish the new EST-SSR markers for analyzing the genetic variation of different population of Salvia miltiorrhiza.

METHODIt was dealt with ESTs newly downloaded from Genbank and that of acquired from HMPL lab EGassembler software, and then carried out SSR loci search and SSR type analysis by SSRIT software. After that, it was designed the EST-SSR primer pairs for PCR amplification condition optimization.

RESULTAbundant and high coverage of SSR loci distribution were found in S. miltiorrhiza with having one SSR per 5.8 kb ESTs. Among them, the occurrences of different repeat units were mainly the di- (63.0%) and tri- (35.5%). The CT/AG was the most frequent motif in dinucleotide motif type and the GAA/TCC was the most frequent motif in trinucleotide repeats. Out off 36 primer pairs, 29 primer pairs (80.5%) were successfully amplified in all samples of S. miltiorrhiza while the rest failed to give PCR products at various annealing temperature and Mg2+ concentrations. The selected primer pairs also showed the polymorphism in samples from different S. miltiorrhiza populations.

CONCLUSIONThe newly establishment of EST-SSR markers showed high SSR loci coverage and genetic polymorphisms in S. miltiorrhiza population. It could be used for genetic variation analysis.

Alleles ; Expressed Sequence Tags ; Gene Frequency ; Genetic Markers ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Salvia miltiorrhiza ; genetics

The application of elicitors, which is currently the focus of research, has been considered as one of the most effective methods to improve the synthesis of secondary metabolites in medicinal plants. Biotic and abiotic elicitors can regulate the secondary metabolic pathways of effective ingredients in Salvia miltiorrhiza. This paper has introduced the research progress about the induction and the regulation mechanism of S. miltiorrhiza by elicitors.
Biosynthetic Pathways ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Salvia miltiorrhiza ; drug effects ; metabolism

Secondary metabolites are produced during the growth and development of plants along with the adaptation of outer environment, as a rule they are the main active ingredients in medicinal plants and ensure the quality of crude drugs. Since biogenesis is quite complex, the production and accumulation of secondary metabolites are influenced by various biotic and abiotic factors either from gene or environments, the complexity may affect quality control of crude drugs and utilization of the active ingredients. The thought and approach adopted in systems biology is a powerful tool to explore biology fully, along with the development of modern molecular biology and information biology, omics integration like genomics, transcriptomics, proteomics, and metabolomics will bring new opportunities for the study of secondary metabolites of medicinal plant. It has great significance to apply this holistic and systematic method in researches on biosynthetic pathway, signal transduction, ecological environment and metabolic engineering of the formation of the secondary metabolites of medicinal plants, and in building secondary metabolite biosynthesis gene expression and regulation system model, in order to explain the origin of the active ingredients of medicinal plants, formation mechanism of the Chinese herbs, metabolic engineering effecting active ingredients of medicinal plants, and the rational exploitation and utilization of resources of medicinal plants systematically.
Models, Biological ; Models, Theoretical ; Plants, Medicinal ; metabolism ; Systems Biology ; methods