Three new polyacetylene glycosides, pilosulynosides A-C (1-3), along with 15 known analogues (4-18), were isolated from the roots of Codonopsis pilosula (Franch.) Nannf. Their structures were determined by 1D and 2D NMR, HRESIMS, and DP4+ probability analysis based on uncalibrated NMR chemical shifts. The promoting effects of all isolated compounds on lysosomal biogenesis were evaluated in HepG2 cells using the LysoTracker Red staining assay. Compounds 1 (pilosulynoside A) and 18 (9-(tetrahydropyran-2-yl)-nonawithout cytotoxicity. Mechanistic studies revealed that these effects were independent of the classical TFEB/TFE3 pathways. Furthermore, compounds 1 and 18 displayed anti-senescence activity in a senescence model of rat cardiac microvascular endothelial cells (CMECs). These findings indicate that polyacetylenes from C. pilosula can promote lysosomal biogenesis via a TFEB/TFE3-independent mechanism and exert anti-senescence effects, offering new lead compounds for therapeutic interventions in senescence and lysosome-related diseases.

In this study, a previously undescribed glutarylimide compound was isolated from Streptomyces sp. JCM 4793. Its structure was evaluated through examinations of the NMR, HREIMS data and ECD calculation. Compound 1 was measured for its cytotoxicities against A549, K562, HepG2, SW480 and MDA-MB-231 cells. Compound 1 exhibited significant inhibitory activity against both K562 and A549 tumor cell lines, with IC50 values of 4.840 +/- 0.329 mu mol/L and 6.036 +/- 0.157 mu mol/L, respectively.

A new aurodox-family compound named 2-methyl-10-hydroxy-A83016F (1) and the known aurodox (2) were isolated from the Streptomyces sp. HKIB0009; their structures were determined through comprehensive analysis of NMR and HRMS data. The antibacterial activities of these compounds against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus were evaluated using the broth microdilution method. The results showed that compound 1 exhibited weak antibacterial activity.

The Ganoderma fungus has been revered for centuries in traditional Chinese medicine and foods with high nutritional value for its purported health benefits.The extracts of Ganoderma applanatum(Pers.)Pat.showed promising protective activity against neurological damage caused by scopolamine in zebrafish.Eleven highly oxygenated lanostane triterpenoids with one or more α,β-unsaturated conjugated moiety,including three previously undescribed compounds appterpenactones A-C(1-3),and a nor-abietane diterpenoid,ganorphenol(4),together with related congeners were obtained from the fruiting bodies of G.applanatum.The structures and absolute configurations of the previously undescribed compounds were elucidated by analysis of nuclear magnetic resonance(NMR)spectra,quantum chemical calculations of NMR and electronic circular dichroism spectra,and X-ray crystallographic data.Compound 1 shares an unusual 6/6/5/6/5 ring system scaffold,while compound 4 represents a rearranged aromatic diterpenoid with rare ortho-dimethyl groups.All compounds were evaluated for their neuroprotective activity in glutamate-induced mouse hippocampal neuronal cell line(HT-22 cells).Ganorphenol(4)and applanoic acid C(6)demonstrated significant neuroprotective activity in inhibiting glutamate-induced HT22 cell death.Biochemical assays suggest that applanoic acid C may exert protective effects by activating the Nrf2/HO-1 pathway.Moreover,the further mechanistic study revealed that ganorphenol(4)can exert neuroprotective effects through the PI3K-AKT-mTOR pathway.Collectively,comprehensive experiments and molecular docking studies demonstrated that compounds 4 and 6 are potential neuroprotective agents.These findings provide valuable insights into the actions of trace bioactive components from edible materials and contribute to the broader understanding of neuroprotective compounds.

Three new naphthomycin derivatives were isolated and identified from Streptomyces sp. HKIB0008, and were designated as naphthomycin R (1), naphthomycin S (2), and naphthomycin T (3). Their structures were elucidated using a combination of spectroscopic techniques, including high-resolution mass spectrometry, and NMR. The naphthoquinone core of 1 underwent carbon-carbon bond cleavage, resulting in a novel structural feature, and a corresponding Baeyer-Villiger oxidation mechanism was proposed. Compounds 2 and 3 possess a complex side chain when compared to known cystine modification on the naphthalenoid core as in the case of naphthomycins I and J. In addition, the minimum inhibitory concentration (MIC) assays for these compounds were conducted.

The activation of conventional (α) and novel (δ) protein kinase C (PKC) isoforms promotes lysosomal biogenesis, a critical process for clearance of pathogenic protein aggregates including β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in neurodegenerative disorders. Notably, PKC activators HEP14/15, characterized by 20-methyl moiety, fail to establish classical C1B domain pharmacophore interactions, suggesting a non-canonical activation mechanism. In this study, structural diversification of 20-deoxyingenol through esterification and acetonide protection yielded 18 new derivatives ( 2–19 ). Systematic screening revealed their lysosome-promoting activities, with structure–activity relationship analysis identifying compounds 4 and 18 as superior autophagy inducers. At 20 μM, these derivatives enhanced autophagic flux by 2.45-fold and 2.31-fold versus vehicle control. Moreover, compounds 4 and 18 exhibited a dose-dependent increase in lysosome numbers, promoted TFEB nuclear translocation, and enhanced lysosome-mediated lipid droplet clearance. Western blot analysis further revealed that compounds 4/18 upregulated proteins associated with the autophagy-lysosome system, suggesting their potential as promising autophagy inducers. Mechanistically, molecular docking simulations indicated thier high-affinity binding to PKCδ, which may explain their autophagy-enhancing properties. Graphical Abstract

Glutarimide-containing polyketides usually exhibit anti-fungi activity, which was well exampled by cycloheximide. In our work, three new polyketide structures, 12-amidestreptimidone (1), 12-carboxylstreptimidone (2) and 3-(5S,8R)-(2-amino-2-oxoethyl-2'-methoxy-2'-oxoethyl)-8,10-dimethyl-7-oxododeca-5-hydroxy-9E,11-diolefin (3) were isolated from Streptomyces sp. JCM 4793. 3 without the glutarimide moiety is not active against fungi as expected, while 1 bearing the amide moiety is much more active than its carboxylic form 2. Here we report the isolation, structural elucidation, antifungal activity, and proposed biosynthesis pathway of 1-3.

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase SpeF and P450 monooxygenase SpeG, is identified in the biosynthesis of spiro polycyclic alkaloids (+)-notoamide B and its diastereomer (+)-versicolamide B. Using notoamide E as a substance, SpeF/SpeG metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-mA with dienyl iminium unit. Subsequently, (+)-notoamide B and (+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

Tetranortriterpenoids are the major secondary metabolites in traditional Chinese medicine from family Meliaceae and Rutaceae,which structurally featured by diverse carbon skeletons and highly oxidized degree.Two new tetranortriterpenoids,walsurobustones F(1)and G(2),were isolated from the leaves of Walsura robusta.Their structures were elucidated by 1D NMR,2D NMR,and MS spectra.Structurally,1 and 2 are two geometric isomers that differ at position C-22.Both 1 and 2 showed obvious antitumor activity against the cancer cell lines HL-60,SMMC-7721,A-549,MCF-7,and SW480.These findings suggest that walsurobustones F(1)and G(2)have the potential to be used as anti-cancer agents.

Four new Myrioneuron alkaloids, named mysumamines A-D (1-4), together with six known compounds (5-10), were isolated from the aerial parts of Mycetia effusa (syn. Myrioneuron effusum (Rubiaceae)). Among these natural products, compounds 1-3 are undescribed tricyclic Myrioneuron alkaloids and compound 4 is a new hexacyclic Myrioneuron alkaloid. The structures of these new compounds were elucidated by MS, 1D- and 2D NMR spectral analysis.

The present study aimed to evaluate the antifungal activities of Eupatorium adenophorum against four strains of wood-decaying fungi, including Inonotus hispida, Inonotus obliquus, and Inonotus cuticularis. Bioguided isolation of the methanol extract of E. adenophorum by silica gel column chromatography and high-performance liquid chromatography afforded six cadinane-type sesquiterpenes. Their structures were identified by nuclear magnetic resonance and MS analyses. According to the antifungal results, the inhibition rate of the compound was between 59.85 % and 77.98 % at a concentration of 200 μg/mL. The EC50 values ranged from 74.5 to 187.4 μg/mL.

One new pepluane-type diterpenoid, pepluenone (1), and four known compounds were isolated from the whole plant of Euphorbia peplus L. Compound 1 possesses a 5/6/5/6 tetracyclic skeleton with a unique aromatic ring D. Its structure was determined based on spectroscopic data and X-ray crystallography. The biogenetic pathway of 1 was proposed, in which chemical transformation verified the aromatization step. In vitro anti-inflammatory activity tests indicated that Compounds 1 and 3 had a strong inhibitory effect on releasing NO from mouse macrophage RAW264.7 induced by LPS.

Five new toosendanin limonoids with highly oxidative furan ring walsurobustones A-D ( 1–4 ), and one new furan ring degraded limonoid walsurobustone E ( 5 ) together with one known compound toonapubesic acid B ( 6 ) were isolated from the leaves of Walsura robusta. Their structures were elucidated by NMR and MS data. Especially, the absolute configuration of toonapubesic acid B ( 6 ) was confirmed by X-ray diffraction study. Compounds 1–6 exhibited good cytotoxicity against the cancer cell lines HL-60, SMMC - 7721, A - 549, MCF - 7, and SW480.

Bacterial aromatic polyketides are usually biosynthesized by the type II polyketide synthase (PKS-II) system. Advances in deoxyribonucleic acid (DNA) sequencing, informatics, and biotechnologies have broadened opportunities for the discovery of aromatic polyketides. Meanwhile, metagenomics is a biotechnology that has been considered as a promising approach for the discovery of novel natural products from uncultured bacteria. Here, we cloned a type II polyketide biosynthetic gene cluster (BGC) from the soil metagenome, and the heterologous expression of this gene cluster in Streptomyces coelicolor M1146 resulted in the production of three anthraquinones, two of which (coelulatins 2 and 3) had special hydroxymethyl and methyloxymethyl modifications at C2 of the polyketide scaffold. Gene deletion and in vitro biochemical characterization indicated that the HemN-like radical S-adenosyl-L-methionine (SAM) enzyme CoeI exhibits methylation and is involved in C2 modification.

A type II polyketide synthase biosynthetic gene cluster (amd) containing three P450 genes was identified from a soil metagenomic library, and novel benz[h]isoquinoline-desferrioxamine B conjugated compound amodesmycins were isolated from Streptomyces albus J1074 harboring the amd gene cluster. Genetic evidence showed that the benz[h]isoquinoline part and desferrioxamine B part in amodesmycins were derived from the amd gene cluster and S. albus J1074, respectively, while P450 enzymes played critical roles in the conjunction of these two parts.

Investigation of the alkaloids from Myrioneuron effusum leads to the isolation of myrionsumamide A (1), a pair of enantiomeric alkaloids with an unprecedented tetracyclic system skeleton. These two alkaloids were separated by chiral HPLC with a ratio of 3 : 5 from the scalemic mixture. Their structures including absolute configurations were determined by NMR spectroscopy, X-ray diffraction data and ECD calculations. Both (+)-1 and (-)-1 showed antibacterial activity against Staphylococcus aureus with MIC at 7.81 mu g ml(-)(1).

Abstract Fungal prenylated indole alkaloids are a group of biologically diverse natural products featuring a bicyclo[2.2.2]diazaoctane ring system and densely functionalized indole-derived units. However, the detailed mechanisms underlying the assembly of the 2H-pyran moiety and stereochemically diversified bicyclo[2.2.2]diazaoctane systems remain uncharacterized. Herein, we report that the spe gene cluster governs the biosynthesis of notoamide B and its congeners (1–6) in Aspergillus ochraceus. In particular, SpeE, a flavoprotein monooxygenase (FPMO), catalyzed the formation of the 2H-pyran moiety; SpeF and SpeG worked together to produce active unstable intermediates, the 17S-hydroxy-2R,3R-epoxide of notoamide E (16), followed by the sequential inverse electronically demanded hetero-Diels-Alder (IEDHDA) reaction and semipinacol rearrangement (SPR) to construct the bicyclo[2.2.2]diazaoctane core and spiro-oxindole moiety in 1–6. Furthermore, enzymatic and nonenzymatic HDA and SPR steps were distinguished via chemical computations and metabolite profile analysis.

Three undescribed jatrophane diterpenoids, named euphpepluones P-R (1–3), were isolated from the whole plant Euphorbia peplus. The structures of these compounds were elucidated by spectroscopic methods. The absolute configuration of 1 was further assigned by X-ray crystallographic analysis. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 2 and 6 exhibited significant inhibition of autophagic flux.

As bacterial natural products have been proved to be the most important source of many therapeutic medicines, the need to discover novel natural products becomes extremely urgent. Despite the fact that the majority of bacterial species are yet to be cultured in a laboratory setting, and that most of the bacterial natural product biosynthetic genes are silent, “metagenomics technology” offers a solution to help clone natural product biosynthetic genes from environmental samples, and genetic engineering enables the silent biosynthetic genes to be activated. In this work, a type II polyketide biosynthetic gene cluster was identified from a soil metagenomic library and was activated by over-expression of a SARP regulator gene in the gene cluster in Streptomyces hosts. A new tetracenomycin type compound tetracenomycin Y was identified from the fermentation broth. This study shows that metagenomics and genetic engineering could be combined to provide access to new natural metabolites.