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Peridecalins C and D (1 and 2), one decalin and one oxygen-decalin containing polyketide-amino acid hybrids with 5/6/6 ring system, was isolated from a genetic mutant of Periconia sp. F-31. Their structures were elucidated through extensive spectroscopic data analysis, including 1 D/2D NMR and HR-MS spectra. Biosynthetically, two proposed Diels-Alder reactions are supposed to be involved in the skeleton construction of 1 and 2.

One new eremophilane sesquiterpene periconianone L (1), together with four known guaiane-type sesquiterpenes 4,10,11-trihydroxyguaiane (2), (-)-guai-1(10)-ene-4α,11-diolhydroxymecuration (3), guaidiol A (4), and epi-guaidiol A (5) were isolated from the endophytic fungus Periconia sp. F-31. The structure of the new compound was established by spectroscopic methods, including UV, IR, HRESIMS, and extensive NMR techniques. Compound 3 was isolated as natural product for the first time.

Three pairs of enantiomeric bibenzyl dimers, (±)-dengratiols E-G [(±)-1-3], were obtained through various chromatographic techniques including chiral HPLC, from the ethanol extract of Dendrobium gratiosissimum. Their structures were elucidated to be R-(+)-1 and S-(-)-1, R-(+)-2 and S-(-)-2, and αR, α'R-(-)-3 and αS, α'S-(+)-3 on the basis of the extensive spectroscopic data and ECD analyses, respectively. The isolated enantiomerically pure along with their racemic forms showed moderate cytotoxicity against human HCT116, U87-MG, HepG2, BGC823, and PC9 cancer cell lines (IC

Hyperforin is a representative polycyclic polyprenylated acylphloroglucinols (PPAPs) that exerts a variety of pharmacological activities. The complete biosynthesis pathway of hyperforin has not been elucidated due to its complex structure and unclear genetic background of its source plants. This mini-review focuses on the bioactivity and biosynthesis of hyperforin. These analyses can provide useful insights into the biosynthesis investigations of hyperforin and other PPAPs with complex structures.

The biosynthesis of blasticidin S has drawn attention due to the participation of the radical SAM enzyme BlsE. The original assignment of BlsE as a radical mediated, redox neutral decarboxylase is unusual, because this reaction appears to serve no biosynthetic purpose and would need to be reversed by a subsequent carboxylation step. Furthermore, with the exception of BlsE, all other radical SAM decarboxylases reported to date are oxidative in nature. Careful analysis of the BlsE reaction, however, demonstrates that BlsE is not a decarboxylase but instead a lyase that catalyzes the dehydration of cytosylglucuronic acid (CGA) to form cytosyl-4′-keto-3′-deoxy-d-glucuronic acid, which can rapidly decarboxylate nonenzymatically in vitro. Analysis of substrate isotopologs, fluorinated analogs, as well as computational models based on X-ray crystal structures of the BlsE·SAM (2.09 Å) and BlsE·SAM·CGA (2.62 Å) complexes suggests that BlsE catalysis likely proceeds via direct elimination of water from the CGA C4′ α-hydroxyalkyl radical as opposed to 1, 2-migration of the C3′-hydroxyl prior to dehydration. Biosynthetic and mechanistic implications of the revised assignment of BlsE are discussed.

Bistachybotrysins W-Y (1–3), three new phenylspirodrimane dimers with a 6/7 oxygen heterocycle as the linkage, were isolated from Stachybotrys chartarum CGMCC 3.5365. The structures of 1–3 were elucidated through extensive spectroscopic data analysis, including 1D/2D NMR, HR-ESI-MS, and ECD spectra. Compounds 1 and 3 displayed moderate cytotoxic activity against human tumor cell lines HCT116, Daoy, and HepG2 with IC50 values ranging from 5.9 to 9.8 μM.

Bistachybotrysin K (1), one new phenylspirodrimane dimer with a central 6/7 oxygen heterocycle core, was isolated from the fungus Stachybotrys chartarum CGMCC 3.5365. Its structure was eluc...

Many O-glucuronides exhibiting various pharmacological activities have been found in nature and in drug metabolism. The glucuronidation of bioactive natural products or drugs to generate glucuronides with better activity and druggability is important in drug discovery and research. In this study, by using two uridine diphosphate (UDP)-dependent glucuronosyltransferases (GATs, UGT88D4 and UGT88D7) from plants, we developed two glucuronidation approaches, pure enzyme catalysis in vitro and recombinant whole-cell catalysis in vivo, to efficiently synthesize bioactive O-glucuronides by the glucuronidation of natural products. In total, 14 O-glucuronides with different structures, including flavonoids, anthraquinones, coumarins, and lignans, were obtained, 7 of which were new compounds. Furthermore, one of the biosynthesized O-glucuronides, kaempferol-7- O-β-d-glucuronide (3a), potently inhibited protein tyrosine phosphatase (PTP) 1B with an IC50 value of 8.02 × 10-6 M. Some of the biosynthesized O-glucuronides also exhibited significant antioxidant activities.

Bistachybotrysins D and E (1 and 2), one stereoisomeric pair of phenylspirodrimane dimers, were isolated from Stachybotrys chartarum CGMCC 3.5365. They represent novel phenylspirodrimane dimers with a central [6,5,6]-tricyclic carbon scaffold containing a cyclopentanone core. The structures of 1 and 2 were elucidated through extensive spectroscopic data analysis, and their absolute configurations were characterized by calculated electronic circular dichroism (ECD). Compounds 1 and 2 displayed potent cytotoxic activity against the four human tumor cell lines HCT116, BGC823, Daoy and HepG2 with IC50 values ranging from 6.7 μmol/L to 11.6 μmol/L. Furthermore, a plausible biogenetic pathway for 1 and 2 is proposed.

Enzymatic glycosylation catalyzed by glycosyltransferases (GTs) has great potential in creating diverse novel and bioactive glycosides. Herein, three new GTs (UGT84A33, UGT71AE1 and UGT90A14) from Carthamus tinctorius exhibited robust catalytic promiscuity to benzylisoquinoline alkaloids, and were used as enzymatic tools in glycosylation of bioactive benzylisoquinoline alkaloids. Seven novel benzylisoquinoline alkaloids O-glycosides were synthesized with high efficiency. These studies indicate the significant potential of promiscuous GTs in synthesis of benzylisoquinoline alkaloids glycosides for drug discovery.

Prenylflavonoids are valuable natural products that have diverse biological properties, and are usually generated biologically by multiple metabolic enzymes in nature. In this study, structurally diverse prenylflavonoids were conveniently synthesized by enzymatic catalysis by combining GuILDT, a regiospecific chalcone prenyltransferase, and GuCHI, a stereospecific chalcone isomerase that has promiscuous activity for both chalcones and prenylchalcones as substrates. Our findings provided a new approach for the synthesis of natural/unnatural bioactive prenylflavonoids, including prenylchalcones and optical prenylflavanones with chalcone origins., Graphical abstract This study demonstrates that structurally diverse prenylflavonoids were conveniently synthesized through promiscuously enzymatic catalysis by combining a regiospecific chalcone prenyltransferase and a stereospecific chalcone isomerase.fx1

Eight novel acetophenone mono- and bis-C-glucosides were obtained by whole cells harboring an engineered C-glycosyltransferase. Optimization of the fed-bath process improved the yield of 4a to 0.97 mg/mL with 95% conversion rate, which is 2.9-fold higher than that of the single-bath. Four mono-C-glucosides (1a–4a) exhibited potent SGLT2 inhibitory activities with IC50 values at 10−6 M. These findings provide a cost-effective and practical synthetic strategy to produce structurally diverse and novel bioactive C-glucosides for drug discovery.

C-Glycosyltransferases (CGTs) are powerful tools for the C-glycosylation of natural and unnatural products. However, CGTs able to catalyze bis-C-glycosylation are very rare and the key amino acids of which have not been uncovered. Here, we discovered a C-glycosyltransferase MiCGTb from Mangifera indica that has the capacity for bis-C-glycosylation. Further studies on active-site motifs revealed that I152 of MiCGTb was the critical amino acid residue for the second C-glycosylation and its S60/V100/T104 residues were pivotal for bis-C-glycosylation activity. Moreover, we developed a panel of variants with acceptor and donor promiscuity by site-directed mutagenesis. Among these variants, a mutant MiCGT-E152L displayed a broader acceptor scope for bis-C-glycosylation, and three mutants of MiCGTb exhibited sugar donor promiscuity toward structurally varied α-d- and β-l-glycosyl donors. Our work provides insights into the pivotal amino acid residues of CGTs for bis-C-glycosylation and biocatalytic tools to effi...

Bistachybotrysins A–C ( 1 – 3 ), three phenylspirodrimane dimers representing an unusual [6,6,7,6]-tetracyclic skeleton with a central 2,10-dioxabicyclo[4.3.1]decan-7-ol core fused with two phenyl units, were isolated from a fungal strain, Stachybotrys chartarum CGMCC 3.5365. The structures of 1 – 3 were elucidated through extensive spectroscopic data analysis, including Mo 2 (AcO) 4 -induced and calculated electronic circular dichroism (ECD). 1 and 2 exhibited potent cytotoxicity against four human tumor cell lines with IC 50 values in the range of 2.8–7.5 μM. Furthermore, a possible biogenesis for 1 – 3 is proposed.

Harzianols A−E (2–6) and harziane acid (7), six new oxidized derivatives of harzianone (1), were obtained from the microbial transformation by a bacterial strain Bacillus sp. IMM-006. The structures of these products, including the stereochemistry, were elucidated by extensive spectroscopic analysis. The absolute configuration of 2 was unambiguously determined by single-crystal X-ray diffraction. Moreover, a plausible bioconversion pathway was proposed.

The microbial transformation of glycyrrhetinic acid (1) by Cunninghamella blakesleana CGMCC 3.970 led to the production of five new metabolites (2–6). The structures of the metabolites were determined by extensive spectroscopic (HR-ESIMS, 1D and 2D NMR) data analyses. The involved reactions exhibited specific hydroxylations at C-24, C-7, and C-15, and oxidation at C-3. Moreover, compounds 2, 5, and 6 showed significant neural anti-inscommatory activity by inhibiting lipopolysaccharide-induced NO production in mouse microglia BV2 cells with IC50 values of 0.76, 0.94, and 0.16 μmol/L, respectively.

Four new farnesylated isoindolinone derivatives, named stachybotrysams A–D ( 2 – 5 ), and one new farnesyl-cyclized analogue, named stachybotrysam E ( 6 ), as well as one known congener ( 1 ), were isolated from the filamentous fungus Stachybotrys chartarum CGMCC 3.5365. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and by comparison with reported data. Compounds 2–4 exhibited significant HIV-inhibitory activity with IC 50 values of 9.3, 1.0, and 9.6 μ M, respectively.

Seven new phenylspirodrimane derivatives named stachybotrysins A–G (2–8), together with five known compounds (1, 9–12), were isolated from Stachybotrys chartarum CGMCC 3.5365. Stachybotrysin D (5) is the first reported example of a naturally occurring alcoholic O-sulfation of a phenylspirodrimane, and stachybotrysins F and G (7 and 8) are the first examples possessing an isobenzotetrahydrofuran ring with an acetonyl moiety attached. The structures of these compounds were elucidated on the basis of extensive spectroscopic data analysis and by comparison with reported data. The absolute configurations of 1–8 were determined by X-ray single-crystal diffraction, electronic circular dichroism (ECD), and calculated ECD. Compounds 1 and 8 displayed anti-HIV activity with IC50 values of 15.6 and 18.1 μM, respectively, and 2, 7, 9, and 11 showed inhibitory effect on influenza A virus with IC50 values ranging from 12.4 to 18.9 μM.

Enzymatic glucosylation of unnatural products by natural glycosyltransferases (GTs) has great potential in creating novel and bioactive glucosides. A new GT (AaGT3) from Aloe arborescens exhibited catalytic promiscuity and high efficiency to diverse unnatural naphthols. By combing the substrate flexibility and catalytic reversibility of AaGT3, a cost-effective enzymatic approach to novel and bioactive unnatural glucosides was established. These studies indicate the significant potential of promiscuous natural GTs in synthesis of unnatural bioactive glucosides in drug discovery.

Five monoterpenoids were isolated from the endophytic fungus Periconia sp. F-31, including three new carene-type monoterpenoids, 2-carene-5,8-diol (1), 2-carene-8,10-diol (2), 2-carene-8-acetamide (3), one new menthene-type monoterpenoid 8-hydroxy-1,7-expoxy-2-menthene (4), and one known monoterpenoid anethofuran (5). The structures of all compounds were elucidated based on a comprehensive spectroscopic data analysis, electronic circular dichroism (ECD), and calculated ECD.

Eleven new sesquiterpenoids, including eight cadinane-type sesquiterpenoids, Ganodermanol A-H (1-8), and three eudesmane-type sesquiterpenoids, Ganodermanol I-K (9-11), together with three known compounds (12-14), were isolated from the cultured mycelia of Ganoderma capense. Their structures and absolute configurations were identified through combined extensive spectroscopic analysis, circular dichroism (CD), and Mo2(AcO)4-induced CD. Compounds 4 and 9 exhibited moderate cytotoxic activity against the human cancer cell line HCT116 with IC50 values of 16.6 and 12.2μM, respectively.

Icariin (1a), a 7-O-glycosylated flavonoid glycoside, is recognized as the major pharmacologically active ingredient of Epimedium plants, which have been used in traditional Chinese medicine for thousands of years. However, no glycosyltransferase (GT) responsible for the 7-O-glycosylation of flavonoids has been identified from Epimedium plants to date. Herein, a GT, Ep7GT, was identified from E. pseudowushanense B. L. Guo, which can regiospecifically transfer a glucose moiety to baohuoside (1) at 7-OH to form icariin (1a). Ep7GT showed a rare broad donor substrate spectrum, including UDP-glucose, UDP-xylose, UDP-N-acetylglucosamine, UDP-rhamnose, UDP-galactose, UDP-glucuronic acid and TDP-glucose. Moreover, two new derivatives of icariin (1a), 7-O-β-D-[2-(acetylamino)-2-deoxy-glucopyranosyl]-baohuoside (1b) and 7-O-β-D-xylosyl-baohuoside (1c), were biosynthesized by using Ep7GT in vitro. Engineered Escherichia coli harbouring Ep7GT was constructed, and 10.1 μg mL−1 icariin (1a) was yielded by whole-cell biotransformation with baohuoside (1) as the substrate. The present work not only characterizes the GT responsible for the 7-O-glycosylation in the biosynthesis of icariin in Epimedium plants, but also indicates the significant potential of an enzymatic approach for the production of glycosylated baohuoside derivatives with different sugar moieties. What's more, these findings also provide a promising alternative for producing natural/unnatural bioactive flavonoid glycosides by metabolic engineering.

Bistachybotrysins F-J (1–5), five new phenylspirodrimane dimers with a central cyclopentanone core were isolated from Stachybotrys chartarum CGMCC 3.5365. The structures of 1–5 were elucidated through extensive spectroscopic data analysis, including 1D/2D NMR, HR-MS, and ECD spectra. Compounds 3–5 displayed moderate cytotoxic activity against the cell lines HCT116, NCI-H460, and HepG2 with IC50 values ranging from 9.1 to 12.2 μM, making them promising as lead compounds for drug research and discovery.

Dengratiol A (1), an unprecedented bibenzyl derivative bearing a tropolone unit together with three pairs of bibenzyl enantiomers (±)-dengratiols B–D [(±)-2–(±)-4], were isolated from Dendrobium gratiossimum Rchb.f. The resolution of enantiomers was performed with chiral HPLC. Their structures were characterized by extensive spectroscopic data analysis and calculated electronic circular dichroism (ECD). A hypothetical biosynthetic pathway for 1 is proposed. Biological assay revealed that (−)-2 showed moderate antiviral effect against IAV with IC50 value of 6.3 μM, and (±)-2 displayed cytotoxic activities against five human tumor cell lines with IC50 values ranging from 15.5 to 42.5 μM.

Periconones B–E (1–4), four new polyketide–terpenoid hybrid molecules were isolated from the endophytic fungus Periconia sp. F-31. Their structures and absolute configurations were established by extensive spectroscopic data analysis and electronic circular dichroism (ECD). Compound 4 exhibited in vitro cytotoxic activity against the human MCF-7 tumor cell line with an IC50 value of 4.2 μmol/L, and compound 1 displayed anti-HIV activity with an IC50 value of 18.0 μmol/L.

A new glycosyltransferase (UGT71E5) from Carthamus tinctorius exhibited a robust promiscuity towards 30 structurally diverse drug-like aromatic amine scaffolds, making it the first reported glycosyltransferase capable of catalyzing N-glycosylation with multiple diverse nitrogen-heterocyclic aromatic compounds. The catalytic promiscuity and reversibility of UGT71E5 was exploited to generate the rare N-glycoside from the abundant O-glycoside with high efficiency. These findings demonstrate the significant potential of UGT71E5 in the enzymatic synthesis of diverse bioactive N-glycosides.

Two new cytochalasans, periconiasin I (1) with 9/6/5 tricyclic ring, and periconiasin J (2) with 5/6/6/5 tetracyclic ring, were isolated from the endophytic fungus Periconia sp. F-31. Their structures including absolute configurations were elucidated through extensive spectroscopic analyses, calculated ECD, and the circular dichroism data of the [Rh2(OCOCF3)4] complex. Compound 1 showed in vitro cytotoxicity against human MCF-7 tumor cell line with an IC50 value of 4.8 μM, compound 2 exhibited weak anti-HIV activity with an IC50 value of 25.0 μM.

Nine new polyoxygenated eremophilane sesquiterpenes, periconianones C-K (1-9), including one unusual isoeremophilane sesquiterpene, periconianone C (1), and four trinor-eremophilane sesquiterpenes, periconianones H-K (6-9), were isolated from the endophytic fungus Periconia sp. F-31. Compound 1 is the first furan-type isoeremophilane reported containing a linkage of C-8/C-11 and a 7,12-epoxy moiety. These compound structures, including absolute configurations, were elucidated through extensive spectroscopic data analysis, electronic circular dichroism, Mo2(AcO)4-induced circular dichroism, and single-crystal X-ray diffraction (Cu Kα). Compounds 2, 5, and 9 showed inhibition effects on lipopolysaccharide-induced NO production in BV2 cells by 10.2%, 18.3%, and 16.1% at a concentration of 1.0 μM, respectively, which is comparable to the positive control curcumin (12.9% at 1.0 μM).

Two new harziane diterpenoids, named (9 R ,10 R )-dihydro-harzianone ( 1 ) and harzianelactone ( 2 ), were isolated from the endophytic fungus Trichoderma sp. Xy24 by using various column chromatography techniques. Their structures were determined on the basis of extensive spectroscopic (HR-ESI-MS, 1D NMR, 2D NMR and CD) analyses. Among them, 1 was the reductive product of harzianone and 2 was the Baeyer–Villiger monooxygenase catalyzed oxidation product of harzianone. Compound 1 exhibited cytotoxic activity against HeLa and MCF-7 cell lines with IC 50 values of 30.1 μmol/L and 30.7 μmol/L, respectively.

The data included in this paper are associated with the research article entitled “Sesquiterpenoids from the cultured mycelia of Ganoderma capense ” [1] . 1 H NMR, 13 C NMR, DEPT, HSQC, 1 H– 1 H COSY, HMBC, NOESY, HRESIMS, and IR spectra of Ganodermanol A–H ( 1 – 11 ), together with Mo 2 (AcO) 4 -induced CD spectrum of Ganodermanol A, CD spectra of Ganodermanol D–E were included in the Data in Brief article. In addition, the cytotoxicities and anti-HIV-1 activity of isolated compounds were also included in the Data in Brief article.

Six new Diels-Alder type adducts, morusalisins A-F (1–6), were isolated from Morus alba cell cultures. The structures of 1–6 were determined by extensive spectroscopic data analysis, including HRESIMS, NMR, and ECD experiments. Furthermore, compounds 1–6 exhibited potent protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values ranging from 1.14 to 2.24 μM, making them promising as bioactive compounds for anti-diabetic drug discovery.

Various bioactive polyketides have been found in Aloe barbadensis. However, the polyketide synthases (PKSs), which participate in biosynthesis of polyketides in A. barbadensis remain unknown. In this study, two type III PKSs (AbPKS1 and AbPKS2) were identified from A. barbadensis. AbPKS1 and AbPKS2 were able to utilize malonyl-CoA to yield heptaketides (TW93a and aloesone) and octaketides (SEK4 and SEK4b), respectively. AbPKS1 also exhibited catalytic promiscuity in recognizing CoA thioesters of aromatics to produce unusual polyketides. What Is more, a whole cell biocatalysis system with the capability of producing 26.4 mg/L of SEK4/SEK4b and 2.1 mg/L of aloesone was successfully established.

Three new phenylspirodrimanes derivatives named stachybotrysins H and I (1 and 2) and stachybotrin E (3), together with one known compound stachybotrylactam (4), were isolated from Stachybotrys chartarum CGMCC 3.5365. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Compounds 1 and 2 showed inhibitory effect towards potassium channel Kv1.3 with IC50 values of 13.4 and 10.9 μM, respectively.

The microbial transformation of 14-anhydrodigoxigenin (1) by Alternaria alternata CGMCC 3.577 led to the production of seven new metabolites, 2-8. Their structures were determined by extensive spectroscopic (CD, IR, 1D- and 2D-NMR, and HR-ESI-MS) data analyses. The reactions in the bioprocess exhibited diversity, including specific oxidation, hydroxylation, reduction, epoxidation, and dehydration. In addition, a hypothetical biocatalytic pathway is proposed.

A chemical investigation of callus cultures of Dysosma versipellis led to the isolation of five new flavonol dimers, dysoverines A-E (1-5), together with 12 known compounds (6-17). The structures of new compounds were determined by the extensive spectroscopic data analyses. The biosynthetic pathway of the new compounds was proposed to involve O-methylation, prenylation, and Diels-Alder cycloaddition, which successively occurred in cultured plant cells. Compounds 1-17 exhibited in vitro neuraminidase inhibitory activities with the IC50 values of 31.0-93.9μM.

Prenylated aromatics are produced by aromatic prenyltransferases during the secondary metabolism of bacteria, fungi and plants. The prenylation of nonprenylated precursors can lead to great chemical diversity and extensive biological properties.Aspergillus terreusaromatic prenyltransferase (AtaPT), which has recently been discovered and characterized, is such an enzyme and is responsible for the prenylation of various aromatic compounds. Here, recombinant AtaPT was overexpressed inEscherichia coli, purified and crystallized. Diffraction data were collected to a resolution of 1.71 Å and the crystal belonged to space groupP21212, with unit-cell parametersa= 96.2,b = 135.8,c= 69.5 Å, α = β = γ = 90°. Analysis of the calculated Matthews coefficient and the self-rotation function suggested that there are two AtaPT molecules in the asymmetric unit.

A new polyketide synthase–nonribosomal peptide synthetase (PKS–NRPS) hybrid metabolite, named pericoannosin B (1), was isolated from endophytic fungus Periconia sp. F-31 of the medicinal plant Annona muricata. The structure and absolute configuration were elucidated by means of extensive spectroscopic analyses (HRMS, NMR, IR, and CD).

The enzymatic synthesis of coumarin C-glucosides by an engineered C-glycosyltransferase, MiCGTb-GAGM, was explored in vitro and in vivo. MiCGTb-GAGM exhibited a robust C-glucosylation capability toward structurally diverse coumarin derivatives. The whole-cell bioconversion of MiCGTb-GAGM was exploited for large-scale production of coumarin C-glucosides. Two C-glucosides exhibited potent SGLT2 inhibitory activities with IC50 values at 10-6 M. These findings provide cost-effective and practical synthetic strategies to generate structurally diverse and novel bioactive coumarin C-glycosides for drug discovery.

Glucuronidation is an important and popular metabolic reaction in vivo of drugs. The further evaluation of biological activity and toxicity of glucuronides is necessary in the course of the drug research and development. However, the synthesis of glucuronides is limited by the lack of efficient approach. Herein, we have developed a new glucuronide synthesis method using plant uridine diphosphate-dependent glucuronosyltransferases (UGTs), UGT88D4, UGT88D7, and EpGT8, enabling the convenient preparation for corresponding O-glucuronide metabolites (1a, 2a, 3a, and 3b) in milligram scale of two neurological active agents, IMM-H004 (1) and FLZ (2). Their structures were characterized by spectroscopic data analyses.

From the cultured endophytic fungus Glomerella cingulata isolated from a toxic plant, Gelsemium elegans, one new phenanthrene (1), four new sesquiterpenes (2–5), and three known sesquiterpenes (6–8) were isolated. Their structures were elucidated using spectroscopic methods. Based on the ECD calculations, the absolute configurations of the new compounds were determined. Compounds 2, 4, and 5 inhibited lipopolysaccharide (LPS)-induced NO production in BV2 cells by 50.6, 36.1, and 29.4%, respectively, at 1 μM (positive control curcumin, IC50 = 4.0 μM).

Prenylated flavonoids are attractive specialized metabolites with a wide range of biological activities and are distributed in several plant families. The prenylation catalyzed by prenyltransferases represents a Friedel-Crafts alkylation of the flavonoid skeleton in the biosynthesis of natural prenylated flavonoids and contributes to the structural diversity and biological activities of these compounds. To date, all identified plant flavonoid prenyltransferases (FPTs) have been identified in Leguminosae. In the present study two new FPTs, Morus alba isoliquiritigenin 3'-dimethylallyltransferase (MaIDT) and Cudrania tricuspidata isoliquiritigenin 3'-dimethylallyltransferase (CtIDT), were identified from moraceous plants M. alba and C. tricuspidata, respectively. MaIDT and CtIDT shared low levels of homology with the leguminous FPTs. MaIDT and CtIDT are predicted to be membrane-bound proteins with predicted transit peptides, seven transmembrane regions, and conserved functional domains that are similar to other homogentisate prenyltransferases. Recombinant MaIDT and CtIDT were able to regioselectively introduce dimethylallyl diphosphate into the A ring of three flavonoids with different skeleton types (chalcones, isoflavones, and flavones). Phylogenetic analysis revealed that MaIDT and CtIDT are distantly related to their homologs in Leguminosae, which suggests that FPTs in Moraceae and Leguminosae might have evolved independently. MaIDT and CtIDT represent the first two non-Leguminosae FPTs to be identified in plants and could thus lead to the identification of additional evolutionarily varied FPTs in other non-Leguminosae plants and could elucidate the biosyntheses of prenylated flavonoids in various plants. Furthermore, MaIDT and CtIDT might be used for regiospecific prenylation of flavonoids to produce bioactive compounds for potential therapeutic applications due to their high efficiency and catalytic promiscuity.

Thirteen new glucosides (1–13) of magnolol and honokiol were obtained from specific O-glycosylation by two filamentous fungi, Cunninghamella echinulata AS 3.3400 and Rhizopus japonicus ZW-4. The glucosides' structures were determined on the basis of extensive spectroscopic (HRESIMS, 1D and 2D NMR, and CD) analyses and a chemical method. C. echinulata appeared to transfer a glucosyl moiety to 2-OH of magnolol and honokiol, whereas R. japonicus preferred to regio-specifically transfer a glucosyl moiety to 4′-OH when honokiol was as the substrate. In addition, hydroxylation by C. echinulata and specific 6″-O-acylation of the introduced glucosyl moiety by R. japonicus were observed as minor reactions. Bioassay results indicated that glucosides 1–12 together with magnolol and honokiol at 10 μM attenuated the glutamate-induced toxicity in SK-N-SH cells to levels comparable to the results for MK-801, a positive control. However, the water-solubility of major glucosylated products (1, 8, and 11) increased greatly.