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Scientific Reports Sep 2019Two new harziane diterpene lactones, possessing a 6/5/7/5-fused carbocyclic core containing a lactone ring system, harzianelactones A and B (1 and 2), and five new...
Two new harziane diterpene lactones, possessing a 6/5/7/5-fused carbocyclic core containing a lactone ring system, harzianelactones A and B (1 and 2), and five new harziane diterpenes, harzianones A-D (3-6) and harziane (7), were isolated from the soft coral-derived fungus Trichoderma harzianum XS-20090075. Their structures were determined by extensive NMR spectroscopic data, ECD and OR calculations, as well as X-ray diffraction. The isolated compounds exhibited potent phytotoxicity against seedling growth of amaranth and lettuce. Harziane diterpenes were rarely reported for their remarkably bioactivities, and it was the first report to study the phytotoxicity of harziane diterpenes, which provide a new application of such compounds in agriculture for future research.
Topics: Amaranthus; Animals; Anthozoa; Diterpenes; Herbicides; Lactones; Lactuca; Magnetic Resonance Spectroscopy; Molecular Structure; Plant Weeds; Toxins, Biological; Trichoderma; X-Ray Diffraction
PubMed: 31527674
DOI: 10.1038/s41598-019-49778-7 -
Chemical & Pharmaceutical Bulletin 2023Two new diterpenes named trichoterpene I (1) and trichoterpene II (2) were isolated from the extract from the leaves of Isodon trichocarpus together with 19 known...
Two new diterpenes named trichoterpene I (1) and trichoterpene II (2) were isolated from the extract from the leaves of Isodon trichocarpus together with 19 known diterpenes. Their chemical structures were elucidated on the basis of chemical and physicochemical properties. Among them, oridonin (3), effusanin A (4), and lasiokaurin (9) with the α,β-unsaturated carbonyl moiety showed antiproliferative activities against breast cancer MDA-MB-231 and human astrocytoma U-251 MG cells [i.e., non-cancer stem cells (non-CSCs)] and their cancer stem cells (CSCs) isolated by sphere formation. In particular, compound 4 (IC = 0.51 µM) showed a higher antiproliferative activity against MDA-MB-231 CSCs than against MDA-MB-231 non-CSCs. The antiproliferative activity toward CSCs of compound 4 was equal to adriamycin (positive control, IC = 0.60 µM).
Topics: Humans; Antineoplastic Agents, Phytogenic; Diterpenes; Diterpenes, Kaurane; Doxorubicin; Isodon; Neoplasms; Plant Leaves; Stem Cells
PubMed: 37394598
DOI: 10.1248/cpb.c22-00914 -
The Journal of Physical Chemistry. B Jun 2022Thermostability is the key to maintain the structural integrity and catalytic activity of enzymes in industrial biotechnological processes, such as terpene...
Thermostability is the key to maintain the structural integrity and catalytic activity of enzymes in industrial biotechnological processes, such as terpene cyclase-mediated generation of medicines, chiral synthons, and fine chemicals. However, affording a large increase in the thermostability of enzymes through site-directed protein engineering techniques can constitute a challenge. In this paper, we used ancestral sequence reconstruction to create a hyperstable variant of the -copalyl diphosphate synthase PtmT2, a terpene cyclase involved in the assembly of antibiotics. Molecular dynamics simulations on the μs timescale were performed to shed light on possible molecular mechanisms contributing to activity at an elevated temperature and the large 40 °C increase in melting temperature observed for an ancestral variant of PtmT2. analysis revealed key differences in the flexibility of a loop capping the active site, between extant and ancestral proteins. For the modern enzyme, the loop collapses into the active site at elevated temperatures, thus preventing biocatalysis, whereas the loop remains in a productive conformation both at ambient and high temperatures in the ancestral variant. Restoring a Pro loop residue introduced in the ancestral variant to the corresponding Gly observed in the extant protein led to reduced catalytic activity at high temperatures, with only moderate effects on the melting temperature, supporting the importance of the flexibility of the capping loop in thermoadaptation. Conversely, the inverse Gly to Pro loop mutation in the modern enzyme resulted in a 3-fold increase in the catalytic rate. Despite an overall decrease in maximal activity of ancestor compared to wild type, its increased thermostability provides a robust backbone amenable for further enzyme engineering. Our work cements the importance of loops in enzyme catalysis and provides a molecular mechanism contributing to thermoadaptation in an ancestral enzyme.
Topics: Biocatalysis; Catalytic Domain; Diterpenes; Enzyme Stability; Kinetics; Protein Engineering
PubMed: 35583961
DOI: 10.1021/acs.jpcb.1c10605 -
International Journal of Molecular... Nov 2022Diterpene alkaloids (DAs) are characteristic compounds in , which are classified into four skeletal types: C, C, C, and bisditerpenoid alkaloids. C-DAs are thought to be...
Diterpene alkaloids (DAs) are characteristic compounds in , which are classified into four skeletal types: C, C, C, and bisditerpenoid alkaloids. C-DAs are thought to be the precursor of the other types. Their biosynthetic pathway, however, is largely unclear. Herein, we combine metabolomics and transcriptomics to unveil the methyl jasmonate (MJ) inducible biosynthesis of DAs in the sterile seedling of , the only species in the (Stapf) Rapaics. Target metabolomics based on root and aerial portions identified 51 C-DAs and 15 C-DAs, with 40 inducible compounds. The highest content of C-DA atisine was selected for further network analysis. PacBio Isoform sequencing integrated with RNA sequencing not only provided the full-length transcriptome but also their response to induction, revealing 1994 genes that exhibited up-regulated expression. Further, 38 genes involved in terpenoid biosynthesis were identified, including 7 diterpene synthases. In addition to the expected function of the four diterpene synthases, AgCPS5 was identified to be a new -8,13-CPP synthase in and could also combine with AgKSL1 to form the C-DAs precursor -atiserene. Combined with multiple network analyses, six CYP450 and seven 2-ODD genes predicted to be involved in the biosynthesis of atisine were also identified. This study not only sheds light on diterpene synthase evolution in but also provides a rich dataset of full-length transcriptomes, systemic metabolomes, and gene expression profiles, setting the groundwork for further investigation of the C-DAs biosynthesis pathway.
Topics: Aconitum; Transcriptome; Alkaloids; Diterpenes; Biosynthetic Pathways
PubMed: 36362268
DOI: 10.3390/ijms232113463 -
International Journal of Molecular... Jan 2023Documents on the chemical composition of the soft coral are sparse. The present investigation of the Hainan soft coral resulted in the discovery of six new cembrane...
Documents on the chemical composition of the soft coral are sparse. The present investigation of the Hainan soft coral resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A-F (-) and four known analogs (-). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound was established unambiguously by X-ray diffraction analysis using Ga Kα radiation ( = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound exhibited significant tumor necrosis factor (TNF)- inhibitory activity (IC = 9.5 μmol/L), similar to the positive control dexamethasone (IC = 8.7 μmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC > 50 μmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.
Topics: Animals; Molecular Structure; Anthozoa; Molecular Docking Simulation; Nuclear Magnetic Resonance, Biomolecular; Diterpenes
PubMed: 36768306
DOI: 10.3390/ijms24031979 -
Journal of Natural Products Jan 2018During a 2013 cruise in the Southern Ocean we collected specimens of the octocoral Plumarella delicatissima between 800 and 950 m depth. Five new furanocembranoid...
During a 2013 cruise in the Southern Ocean we collected specimens of the octocoral Plumarella delicatissima between 800 and 950 m depth. Five new furanocembranoid diterpenes, keikipukalides A-E (1-5), the known diterpene pukalide aldehyde (6), and the known norditerpenoid ineleganolide (7) were isolated from the coral. These Plumarella terpenes lack mammalian cytotoxicity, while 2-7 display activity against Leishmania donovani between 1.9 and 12 μM. Structure elucidation was facilitated by one- and two-dimensional NMR spectroscopy and mass spectrometry, and keikipukalides A and E were confirmed by X-ray crystallography.
Topics: Animals; Antarctic Regions; Anthozoa; Crystallography, X-Ray; Diterpenes; Leishmania donovani; Macrocyclic Compounds; Mass Spectrometry; Nuclear Magnetic Resonance, Biomolecular
PubMed: 29260557
DOI: 10.1021/acs.jnatprod.7b00732 -
Molecular Plant Mar 2023The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata, although the molecular...
The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata, although the molecular mechanisms behind clerodane biosynthesis are unknown. Here, we report a high-quality assembly of the 414.98 Mb genome of S. barbata into 13 pseudochromosomes. Using phylogenomic and biochemical data, we mapped the plastidial metabolism of kaurene (gibberellins), abietane, and clerodane diterpenes in three species of the family Lamiaceae (Scutellaria barbata, Scutellaria baicalensis, and Salvia splendens), facilitating the identification of genes involved in the biosynthesis of the clerodanes, kolavenol, and isokolavenol. We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism. Despite the assumed monophyletic origin of clerodane biosynthesis, which is widespread in species of the Lamiaceae, our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae. Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.
Topics: Diterpenes, Clerodane; Scutellaria; Abietanes; Diterpenes; Plants, Medicinal
PubMed: 36639870
DOI: 10.1016/j.molp.2023.01.006 -
Marine Drugs Mar 2022Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A-C (-), one new...
Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A-C (-), one new eunicellin-type diterpene, litophynin K (), and a related known compound, litophynol B () were isolated from the South China Sea soft coral . The structures and absolute configurations of - were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher's method. A plausible biosynthetic relationship of and its potential precursor was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects.
Topics: Animals; Anthozoa; Biological Products; Diterpenes; Lipopolysaccharides; Mice; Models, Molecular; Molecular Structure; Protein Tyrosine Phosphatase, Non-Receptor Type 1; RAW 264.7 Cells; Tumor Necrosis Factor-alpha
PubMed: 35323517
DOI: 10.3390/md20030218 -
Marine Drugs Oct 2023The Arctic-derived fungus sp. D-1 can produce numerous secondary metabolites, and some compounds exhibit excellent biological activity. Seven pimarane-type diterpenes,...
The Arctic-derived fungus sp. D-1 can produce numerous secondary metabolites, and some compounds exhibit excellent biological activity. Seven pimarane-type diterpenes, including three new compounds eutypellenone F (), libertellenone Y (), and libertellenone Z (), and four known compounds (-), were isolated from fermentation broth of sp. D-1 by the OSMAC strategy of adding ethanol as a promoter in the culture medium. Compound has a rare tetrahydrofuran-fused pimarane diterpene skeleton. The anti-inflammatory activity of all compounds was evaluated. Compounds - showed a significant inhibitory effect on cell NO release at 10 μmol/L by in vitro experiments, of which - had inhibitory rates over 60% on nitric oxide (NO) release. Subsequently, the anti-inflammatory activity of - was evaluated based on a zebrafish model, and the results showed that had a significant inhibitory effect on inflammatory cells migration at 40 μmol/L, while and had a significant inhibitory effect at 20 μmol/L. Moreover, compounds - have the same conjugated double bond structure, which may be an important group for these compounds to exert anti-inflammatory activity.
Topics: Animals; Abietanes; Zebrafish; Cell Line, Tumor; Xylariales; Diterpenes; Anti-Inflammatory Agents; Molecular Structure
PubMed: 37888476
DOI: 10.3390/md21100541 -
Marine Drugs Apr 2022A persistent study on soft coral resulted in the characterization of two new cembranolides, tortuolides A and B ( and ), and a new related diterpene, -sarcophytonolide...
A persistent study on soft coral resulted in the characterization of two new cembranolides, tortuolides A and B ( and ), and a new related diterpene, -sarcophytonolide Q. Their structures were determined not only by extensive spectroscopic analysis but also by DFT calculations of ECD and NMR data, the latter of which was combined with statistical analysis methods, e.g., DP4+ and -DP4 approaches. Anti-inflammatory and cytotoxicity activities were evaluated in this study.
Topics: Animals; Anthozoa; Anti-Inflammatory Agents; Diterpenes; Drug Screening Assays, Antitumor; Magnetic Resonance Spectroscopy
PubMed: 35621948
DOI: 10.3390/md20050297