Characterization of SchTPSs Enables Construction of Yeast for the Bioproduction of α-Cadinol and the Related Sesquiterpenes.

Plant volatile sesquiterpenes (PVSs) play important roles in chemical plant defense. However, it is difficult to isolate sufficient PVSs for deep investigations due to their low contents and chemical and physical properties close to those of other lipids. The extracts of L.

Manipulation of IME4 expression, a global regulation strategy for metabolic engineering in .

Metabolic engineering has been widely used for production of natural medicinal molecules. However, engineering high-yield platforms is hindered in large part by limited knowledge of complex regulatory machinery of metabolic network. -Methyladenosine (mA) modification of RNA plays critical roles in regulation of gene expression.

New abietane and tigliane diterpenoids from the roots of and their cytotoxic activities.

Three new abietane and two new tigliane diterpenoids were isolated from the roots Their structures were elucidated by spectroscopic methods and quantum chemical calculation. Compounds and exhibited the inhibitory activities against human cancer cells HeLa and HepG2, with IC ranging from 3.54 to 11.

Rationally engineering santalene synthase to readjust the component ratio of sandalwood oil.

Plant essential oils (PEOs) are widely used in cosmetic and nutraceutical industries. The component ratios of PEOs determine their qualities. Controlling the component ratios is challenging in construction of PEO biotechnological platforms.

Chamaejasnoids A-E, a 2,3-seco-guaiane sesquiterpenoid with a 5/6/7 bridged ring system and related metabolites from Stellera chamaejasme L.

Sixteen guaiane-type sesquiterpenoids were isolated from Stellera chamaejasme L. Among them, chamaejasnoids A-F (1-5) are new compounds. 1 represents the first example of 2,3-seco-guaiane sesquiterpenoid with a 5/6/7 bridged ring system.

Mining of the Genome Leads to Identification of a Biosynthetic Gene Cluster for Fungicidal Sesquiterpenes.

Characterization of cryptic biosynthetic gene clusters (BGCs) from microbial genomes has been proven to be a powerful approach to the discovery of new natural products. However, such a genome mining approach to the discovery of bioactive plant metabolites has been muted. The plant BGCs characterized to date encode pathways for antibiotics important in plant defense against microbial pathogens, providing a means to discover such phytoalexins by mining plant genomes.

A review: biosynthesis of plant-derived labdane-related diterpenoids.

Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring systems derived from labdane-type skeletons, such as abietane, pimarane, kaurane, etc. Due to their various pharmaceutical activities and unique properties, many of LRDs have been widely used in pharmaceutical, food and perfume industries.

Characterization of a Sesquiterpene Synthase Catalyzing Formation of Cedrol and Two Diastereoisomers of Tricho-Acorenol from .

A sesquiterpene synthase gene was identified from the transcriptome of Steud, and the function of its product EfTPS12 was characterized by biochemical experiments and synthetic biology approaches. EfTPS12 catalyzed conversion of farnesyl diphosphate into three products, including cedrol () and eupho-acorenols A () and B () (two diastereoisomers of tricho-acorenol), thereby being named EfCAS herein. The structures of and were determined by spectroscopic methods and comparison of experimental and calculated electronic circular dichroism spectra.

Daphnane-type diterpenoids from Euphorbia fischeriana Steud and their cytotoxic activities.

Two new daphnane-type diterpenoids fischerianin A (1) and fischerianin B (2), as well as two known ones langduin A (3) and langduin A (4), were isolated from the extracts of Euphorbia fischeriana Steud dry roots. Their structures including the absolute stereochemistry were determined by various spectroscopic methods and comparing their experimental and calculated CD spectra. 1 and 2 harbor a ketal group and a 9,13-oxide bridge in their C ring which is rare in daphnane-type diterpenoids.

Characterization of Guaiene Synthases from L. Flowers and Their Application in De novo Production of (-)-Rotundone in Yeast.

Four terpene synthases for the biosynthesis of volatile terpenoids were identified from the transcriptome of L. flowers, including SchTPS1, SchTPS2, SchTPS3, and SchTPS4. Their functions were characterized by synthetic biology approaches in and in vitro enzymatic assays.

Control of Stereoselectivity in Diverse Hapalindole Metabolites is Mediated by Cofactor-Induced Combinatorial Pairing of Stig Cyclases.

Stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by Stig cyclases through a three-step cascade involving Cope rearrangement, 6-exo-trig cyclization, and a final electrophilic aromatic substitution. Reported here is a comprehensive study of all currently annotated Stig cyclases, revealing that these proteins can assemble into heteromeric complexes, induced by Ca , to cooperatively control the stereochemistry of hapalindole natural products.

Green production of silybin and isosilybin by merging metabolic engineering approaches and enzymatic catalysis.

Silymarin extracted from milk thistle seeds, is used for treating hepatic diseases. Silybin and isosilybin are its main components, and synthesized from coupling of taxifolin and coniferyl alcohol. Here, the biosynthetic pathways of taxifolin and coniferyl alcohol were reconstructed in Saccharomyces cerevisiae for the first time.

Reconstruction of the Biosynthetic Pathway of Santalols under Control of the GAL Regulatory System in Yeast.

Sandalwood oil has been widely used in perfumery industries and aromatherapy. Santalols are its major components. Herein, we attempted to construct santalol-producing yeasts.

[Limonoids from seeds of Azadirachta indica and their antibacterial activity].

Fifteen limonoids were isolated from 95% ethanol extracts of the dry seeds of neem( Azadirachta indica) by various column chromatography techniques including silica gel,Pharmadex LH-20 gel and ODS resin. Based on spectroscopic analysis,their structures were determined as nimbocinol( 1),17β-hydroxynimbocinol( 2),1α,3α,7α-triacetylvilasinin( 3),7α-benzoyltrichilinin( 4),1,3-diacetyl-7-tigloyl-12-hydroxyvilasinin( 5),3-deacetylsalannin( 6),1-O-acetyl-1-detigloylsalannin( 7),2'( R),3'-dihydrosalannin( 8),2'( S),3'-dihydrosalannin( 9),2,3-dihydronimbolide( 10),6-homodesacetylnimbin( 11),gedunin( 12),7-deacetyl-7-epi-dihydrogedunin( 13),7-deacetoxy-7α-hydroxygedunin( 14) and nimbinene( 15). Compound 7 is a new natural product.

Enhance production of diterpenoids in yeast by overexpression of the fused enzyme of ERG20 and its mutant mERG20.

Yeast has been widely used for large-scale production of terpenoids. In yeast, modifications of terpenoid biosynthetic pathways have been intensively studied. tHMG1 (encoding the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase of yeast) and UPC2-1 (the G888D mutant of UPC2 encoding a transcription factor) were integrated into yeast chromosome, and ERG9 (the squalene synthase gene of yeast) was knocked down to yield the chassis strain DH02.

Modified substrate specificity of a methyltransferase domain by protein insertion into an adenylation domain of the bassianolide synthetase.

Background: Creating designer molecules using a combination of select domains from polyketide synthases and/or nonribosomal peptide synthetases (NRPS) continues to be a synthetic goal. However, an incomplete understanding of how protein-protein interactions and dynamics affect each of the domain functions stands as a major obstacle in the field. Of particular interest is understanding the basis for a class of methyltransferase domains (MT) that are found embedded within the adenylation domain (A) of fungal NRPS systems instead of in an end-to-end architecture.

Identification of RoCYP01 (CYP716A155) enables construction of engineered yeast for high-yield production of betulinic acid.

Betulinic acid (BA) and its derivatives possess potent pharmacological activity against cancer and HIV. As with many phytochemicals, access to BA is limited by the requirement for laborious extraction from plant biomass where it is found in low amounts. This might be alleviated by metabolically engineering production of BA into an industrially relevant microbe such as Saccharomyces cerevisiae (yeast), which requires complete elucidation of the corresponding biosynthetic pathway.

Four limonoids from Bacillus subtilis-fermented neem seeds and their cytotoxic activity.

Four new limonoids, 7,12-dihydroxyvilasinone (1), vilasindione (2), 4-dehydroxynimbandiol (3) and azadiramide B (4), were isolated from extracts of Bacillus subtilis-fermented neem seeds. Their planar structures and relative configurations were elucidated by spectroscopic methods including UV, IR, MS and NMR, and the absolute stereochemistry was determined by comparing their experimental and calculated CD spectra. 4 is a rare salannin-class limonoid alkaloid.

Effect of Fungal Elicitor on the Production of Terpenoid Indole Alkaloids in Cambial Meristematic Cells.

This study reported the inducing effect of fungal elicitor on biosynthesis of terpenoid indole alkaloids (TIAs) in cambial meristematic cells (CMCs) and its inducing mechanism. According to the results determined by HPLC and HPLC-MS/MS, the optimal condition of the elicitor was as follows: after suspension culture of CMCs for 6 day, 25 mg/L mycelium elicitor were added, and the CMC suspensions were further cultured for another 48 h. In this condition, the contents of vindoline, catharanthine, and ajmaline were 1.

Limonoids from seeds of A. Juss. and their cytotoxic activity.

Four new limonoid-type nortriterpenoids, 1-detigloyl-1--methacryloylsalannin (), 28-deoxo-2,3-dihydronimbolide (), 12-acetoxy-3--acetyl-7--tigloylvilasinin () and 12-acetoxy-3--acetyl-7--methacryloylvilasinin (), along with five known ones, were isolated from seeds of A. Juss. Their structures were elucidated by various spectroscopic methods, including UV, IR, MS, NMR, X-ray crystallography, quantum chemical calculation, as well as by comparison of their spectroscopic data with those reported.

Hapalindole H Induces Apoptosis as an Inhibitor of NF-ĸB and Affects the Intrinsic Mitochondrial Pathway in PC-3 Androgen-insensitive Prostate Cancer Cells.

Background: Prostate cancer presents the highest incidence rates among all cancers in men. Hapalindole H (Hap H), isolated from Fischerella muscicola (UTEX strain number LB1829) as part of our natural product anticancer drug discovery program, was found to be significantly active against prostate cancer cells.

Materials And Methods: In this study, Hap H was tested for nuclear factor-kappa B (NF-ĸB) inhibition and selective cytotoxic activity against different cancer cell lines.

[Limonoids from seeds of Azadirachta indica and their cytotoxic activity].

Eight limonoids were isolated from 95% ethanol extracts of neem(Azadirachta indica) seeds by various chromatographic methods. By comparison of their spectroscopic data with those reported in the literatures, these limonoids were determined as salannin(1), 1-detigloyl-1-isobutylsalannin(2), salannol-3-acetate(3), salannol(4), spirosendan(5), 1-detigloyloxy-3-deacetylsalannin-1-en-3-one(6), nimbin(7) and 6-deacetylnimbin(8). Compounds 2 and 5 were firstly isolated from this genus and 5 represented the only example of its type.

Four New Compounds Obtained from Cultured Cells of Artemisia annua.

Four new compounds obtained from cultured cells of were reported. Products were detected by HPLC-ELSD/GC-MS and isolated by chromatographic methods. The structures of four new compounds, namely 6-hydroxy arteannuin I (), 1-hydroxy arteannuin I (), 2-hydroxy arteannuin J (), and 14-hydroxy arteannuin J (), were elucidated using their physico-chemical properties by NMR and MS data analyses.