Targeting bacterial phospholipids and their synthesis pathways for antibiotic discovery.

Bacterial infections in humans and animals caused by multidrug-resistant (MDR) pathogens pose a serious threat to public health. New antibacterial targets are extremely urgent to solve the dilemma of cross-resistance. Phospholipids are critical components in bacterial envelopes and involve diverse crucial processes to maintain homeostasis and modulate metabolism.

Target Discovery of Dhilirane-Type Meroterpenoids by Biosynthesis Guidance and Tailoring Enzyme Catalysis.

Dhilirane-type meroterpenoids (DMs) featuring a 6/6/6/5/5 ring system represent a rare group of fungal meroterpenoids. To date, merely 11 DMs have been isolated or derived, leaving their chemical diversity predominantly unexplored. Herein, we leverage an understanding of biosynthesis to develop a workflow for discovery of DMs by genome mining, metabolite analysis, and tailoring enzyme catalysis.

Three-dimensional structural alignment based discovery and molecular basis of AtoB, catalyzing linear tetracyclic formation.

Enzymes from the nuclear transport factor 2-like (NTF2-like) superfamily represent a rare group of biocatalysts with diverse catalytic functions facilitating intriguing skeleton formations. However, most proteins of this family remain enigmatic and await further elucidation. In this study, a combination of protein structural alignment with clustering analysis uncovers a new aldolase, AtoB, belonging to the NTF2-like superfamily.

New Meroterpenes from South China Sea Soft Coral .

A chemical investigation of the extracts from the soft coral led to the isolation and identification of four new meroterpenes, brassihydroxybenzoquinone A and B ( and ) and brassinaphthoquinone A and B ( and ), along with two known related meroterpenes ( and ). Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR) spectroscopy, and a comparison with the literature data. All compounds were evaluated for antibacterial activity against six pathogenic bacterial strains and for cytotoxic activity against three cancer cell lines.

Praelolide alleviates collagen-induced arthritis through increasing catalase activity and activating Nrf2 pathway.

Background: Marine diterpenes represent a promising reservoir for identifying potential anti-rheumatoid arthritis (RA) candidates. Praelolide is a gorgonian-derived briarane-type diterpenoid with antioxidative and anti-osteoclastogenetic properties.

Objective: This study aims to evaluate the therapeutic efficacy of praelolide against RA and investigate its underlying mechanisms both in vivo and in vitro.

Discovery of a Hybrid Molecule with Phytotoxic Activity by Genome Mining, Heterologous Expression, and OSMAC Strategy.

Genome mining in association with the OSMAC (one strain, many compounds) approach provides a feasible strategy to extend the chemical diversity and novelty of natural products. In this study, we identified the biosynthetic gene cluster (BGC) of restricticin, a promising antifungal agent featuring a reactive primary amine, from the fungus LZDX-33-4 by genome mining. Combining heterologous expression and the OSMAC strategy resulted in the production of a new hybrid product (), along with -acetyl-restricticin () and restricticinol ().

GC-MS method for simultaneous determination and pharmacokinetic investigation of five volatile components in rat plasma after oral administration of the essential oil extract of .

(PC) is a traditional Chinese medicine (TCM) and food as well as an important essential oil plant in China. PC essential oil exerts pharmacological effects such as anti-inflammatory, anti-oxidant, anti-platelet, anti-thrombotic, and anti-depressant. This study established a reliable and sensitive gas chromatography-mass spectrometry (GC-MS) method for the simultaneous determination of the pharmacokinetics of patchouli alcohol, β-elemene, β-caryophyllene, caryophyllene oxide, and farnesol in the plasma of rats after oral administration of PC essential oil extract.

New Diterpenes and Diterpene Glycosides with Antibacterial Activity from Soft Coral .

Five new biflorane-type diterpenoids, biofloranates E-I (-), and two new bicyclic diterpene glycosides, lemnaboursides H-I (-), along with the known lemnabourside, were isolated from the South China Sea soft coral . Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against and , with MICs ranging from 4 to 64 µg/mL.

Brominated Depsidones with Antibacterial Effects from a Deep-Sea-Derived Fungus sp.

Eleven new brominated depsidones, namely spiromastixones U-Z5 (-) along with five known analogues (-), were isolated from a deep-sea-derived fungus sp. through the addition of sodium bromide during fermentation. Their structures were elucidated by extensive analysis of the spectroscopic data including high-resolution MS and 1D and 2D NMR data.

Irpetones A and B, Anti-Osteoclastic Heptaketides from a Marine Mesophotic Zone Sponge-Associated Fungus sp. NBUF088.

Chemical investigation of sp. NBUF088, associated with an sp. sponge located at an 84 m deep mesophotic zone, led to the discovery of two new heptaketides, named irpetones A () and B ().

Biosynthesis of Epipyrone A Reveals a Highly Specific Membrane-Bound Fungal -Glycosyltransferase for Pyrone Galactosylation.

Epipyrone A is a unique -galactosylated 4-hydroxy-2-pyrone derivative with an antifungal potential from the fungus . We elucidated its biosynthesis via heterologous expression and characterized an unprecedented membrane-bound pyrone -glycosyltransferase biochemically. Molecular docking and mutagenesis experiments suggested a possible mechanism for the heterocyclic -glycosylation and the importance of a transmembrane helix for its catalysis.

Targeted isolation of sorbicilinoids from a deep-sea derived fungus with anti-neuroinflammatory activities.

A chemical fingerprinting approach utilizing LC-MS/MS coupled with 2D NMR data was established to characterize the profile of sorbicilinoid-type metabolites from a deep-sea derived fungus Penicillium rubens F54. Targeted isolation of the cultured fungus resulted in the discovery of 11 undescribed sorbicilinoids namely sorbicillinolides A-K (1-11). Their structures were identified by extensive analyses of the spectroscopic data, including the calculation of electronic circular dichroism and optical rotation for configurational assignments.

Pestanoid A, a Rearranged Pimarane Diterpenoid Osteoclastogenesis Inhibitor from a Marine Mesophotic Zone Chalinidae Sponge-Associated Fungus, sp. NBUF145.

One novel rearranged pimarane diterpenoid, pestanoid A (), and two reported molecules, nodulisporenones A () and B (), were discovered from sp. NBUF145 fungus associated with a 62 m deep mesophotic ("twilight") zone Chalinidae sponge. The structures of - were identified by spectrometry, spectroscopy, quantum-chemical calculations, and X-ray crystallography.

Indoloquinazoline alkaloids suppress angiogenesis and inhibit metastasis of melanoma cells.

Metastasis is the leading cause of cancer-related mortality, targeting angiogenesis emerges as a therapeutic strategy for the treatment of melanoma metastasis. Discovery of new antiangiogenic compounds with specific mechanism of action is still desired. In present study, a bioassay-guidance uncovers the EtOAc extract of a marine-derived fungus Aspergillus clavutus LZD32-24 with significant inhibitory activity against the angiogenesis in Tg (fli1a: EGFP) zebrafish model.

Molecular networking-guided isolation of undescribed antifungal odoriferous sesquiterpenoids from a marine mesophotic zone sponge-associated Streptomyces sp. NBU3428.

Under the guidance of MS/MS-based molecular networking, eight odoriferous sesquiterpenes including two undescribed geosmin-type sesquiterpenoid degradations, odoripenoid A (1) and odoripenoid B (2), and two undescribed germacrane-type sesquiterpenoids, odoripenoid C (3) and odoripenoid (4), together with four known related compounds (5-8) were isolated from the EtOAc extract of the marine mesophotic zone sponge-associated Streptomyces sp. NBU3428. All chemical structures including absolute configurations of these compounds were elucidated by means of HRESIMS, NMR, ECD calculations and single-crystal X-ray diffraction experiments.

Targeted Isolation of Dolabellane Diterpenoids from the Soft Coral Using Molecular Networking.

LC-MS/MS-based molecular networking annotation coupled H NMR detection allowed the depiction of the soft coral to produce a profile of dolabellane-type diterpenoids. Chromatographic separation of the EtOAc fraction resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely, clavirolides J-U (-) Their structures were characterized by the extensive analysis of the spectroscopic data, including the calculated ECD and X-ray diffraction for the configurational assignments. Clavirolides J-K are characterized by a 1,11- and 5,9-fused tricyclic tetradecane scaffold fused with a α,β-unsaturated-δ-lactone, and clavirolide L possesses a 1,11- and 3,5-fused tricyclic tetradecane scaffold, which extend the dolabellane-type scaffolds.

Bio-Active Products from Mangrove Ecosystems.

Mangrove communities represent the coastal habitats located in intertidal zones or brackish waters of tropical and subtropical coastal areas in over 118 countries [...

Discovery of uncommon terpenoids from the South China Sea soft coral Sinularia scabra.

Sinulatones A and B, presented as the unusual carbon skeleton with bicyclo[4.5.0] system, two undescribed sesquiterpenoids, namely sinulalides A and B, along with eight known terpenoids, were isolated from the South China Sea soft coral Sinularia scabra.

Acorane sesquiterpenes from the deep-sea derived fungus with anti-neuroinflammatory effects.

Acorane-type sesquiterpenes comprise a unique class of natural products with a range of pharmaceutical effects. Genome sequencing and gene annotation, along with qRT-PCR detection, demonstrate that the deep-sea derived F-28 fungus shows potential to produce acorane sesquiterpenes. Chromatographic manipulation resulted in the isolation of 20 acorane sesquiterpenes from the large-scale fermented fungal strain.

Briarane-type diterpenoids, the inhibitors of osteoclast formation by interrupting Keap1-Nrf2 interaction and activating Nrf2 pathway.

Chemoinformatic and bioassay-guided fractionation of a gorgonian coral Junceella juncea resulted in the isolation of 45 briarane-type diterpenoids, of which 16 new analogues were characterized. Their structures were identified by extensive analyses of the spectroscopic data. Most isolated briaranes showed significant inhibition against the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in bone marrow-derived macrophages cells (BMMs).

Eremophilane-Type Sesquiterpenes from a Marine-Derived Fungus Penicillium Copticola with Antitumor and Neuroprotective Activities.

Chemical examination of a marine sponge-associated fungus resulted in the isolation of ten undescribed eremophilanes, namely copteremophilanes A-J (-), along with two new glycosides, 5-glycopenostatin F () and 5-glucopenostatin I (). Their structures were determined by extensive spectroscopic data, in association with ECD data and chemical conversions for configurational assignments. Analogs , , and represent a group of uncommon skeletons of eremophilanes with an aromatic ring and a methyl migration from C-5 to C-9, and analogs and are characteristic of a PKS scaffold bearing a glucose unit.

Concise Biosynthesis of Tropone-Containing Spiromaterpenes by a Sesquiterpene Cyclase and a Multifunctional P450 from a Deep-Sea-Derived sp. Fungus.

Spiromaterpenes are a group of rare tropone-containing sesquiterpenes with antineuroinflammatory activity. Herein, we elucidate their biosynthetic pathway in a deep-sea-derived sp. fungus by heterologous expression, biochemical characterization, and incubation experiments.

Equisetin Targets Intracellular through a Host Acting Strategy.

Mammalian cells act as reservoirs of internalized bacteria to circumvent extracellular antibacterial compounds, resulting in relapse and reinfection diseases. The intracellular persistence of renders most traditional antibiotics useless, due to their inadequate subcellular accumulation. To replenish our antibiotic arsenal, we found that a marine-derived compound, equisetin, efficiently eliminates intracellular by potentiating the host autophagy and inducing mitochondrial-mediated ROS generation to clear the invading .

Versicotide G suppresses osteoclastogenesis and prevents osteolysis.

Excessive formation and function of osteoclasts cause various osteolytic bone diseases. Natural products are a potential source for the discovery of new therapeutic candidates to treat bone destruction diseases. In this study, chemical informatics and bioassay guided examination of the marine-derived Aspergillus versicolor F77 fungus chemically resulted in the isolation of seven cyclopeptides, of which versicotides G-J (1-4) are new cyclohexapeptides.