2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a ...diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C
-C
-C
scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å
), PECPS employs a one-pot formation mechanism including a "diketide-CoA intermediate-released" step for the formation of the C
-C
-C
scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
Agarwood has been valued as an exquisite, high-grade fragrant wood since ancient times. Due to the scarcity of high-quality agarwood, it is quite expensive, and the number of original plants has been ...drastically reduced due to overharvesting, including illegal logging. Despite this, a reliable method of agarwood cultivation has yet to be developed. Thus, identifying the biosynthetic pathways of the fragrant components in agarwood might help developers to optimize the culture conditions and create artificial agarwood, by monitoring the expression of the biosynthetic enzymes or their genes. This review presents the characteristics of our recently identified key enzyme, 2-(2-phenylethyl)chromone precursor synthase (PECPS), which generates the common precursor of 2-(2-phenylethyl)chromones (PECs), the main fragrances in agarwood, as well as our reasoning to reach these conclusions. We also discuss the biosynthetic pathway of PECs, unveiled following the identification of PECPS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Viral protein R (Vpr) is an accessory protein in Human immunodeficiency virus‐1 (HIV‐1) and has been suggested as an attractive target for HIV disease treatment. Investigations of the ethanolic ...extracts of twelve Thai herbs revealed that the extracts of the Punica granatum fruits, the Centella asiatica aerials, the Citrus hystrix fruit peels, the Caesalpinia sappan heartwoods, the Piper betel leaves, the Alpinia galangal rhizomes, the Senna tora seeds, the Zingiber cassumunar rhizomes, the Rhinacanthus nasutus leaves, and the Plumbago indica roots exhibited the anti‐Vpr activity in HeLa cells harboring the TREx plasmid encoding full‐length Vpr (TREx‐HeLa‐Vpr cells). Moreover, the investigation of the selected main constituents in Punica granatum, Centella asiatica, A. galangal, and Caesalpinia sappan indicated that punicalagin, asiaticoside, ellagic acid, madecassic acid, madecassoside, zingerone, brazilin, and asiatic acid possessed anti‐Vpr activities at the 10 μM concentration. Among the tested extracts and compounds, the extracts from Centella asiatica and Citrus hystrix and the compounds, punicalagin and asiaticoside, showed the most potent anti‐Vpr activities without any cytotoxicity, respectively.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The therapeutic effects of Δ9-tetrahydrocannabinol (Δ9-THC) can be enhanced by modifications of the pentyl moiety at C-3. The engineering of Cannabis sativa olivetolic acid cyclase and tetraketide ...synthase with F24I and L190G substitutions, respectively, in the biosynthesis of Δ9-THC serves as a platform for the generation of resorcylic acids up to 6-undecylresorcylic acid. These results provide insights into the development of THC analogs with chemically distinct acyl moieties at C-3.
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IJS, KILJ, NUK, PNG, UL, UM
A new phenolic derivative, galeomalate A (1), together with five known structurally related compounds (2‐6), was isolated from the ethyl acetate extract of Galeola nudifolia collected in Vietnam. The ...structures were elucidated by various spectroscopic methods, including 1D and 2D NMR, HR‐ESI‐TOF‐MS, and CD data, and chemical conversion of the sugar moiety. All isolated compounds possessed acetylcholinesterase (AChE) inhibitory activities in a dose‐dependent manner. Among them, compounds 2 and 3 exhibited the first and second highest inhibitory activity on AChE with IC50 values of 122.13 and 125.49 μM, respectively. Compounds 1 and 4–6 inhibited the AChE activity by mixed modes of action comprising competitive and non‐competitive modes, whereas 2 and 3 exerted their inhibitory activities in a competitive manner. Molecular docking analyses suggested that the phenyl‐β‐D‐glucopyranoside unit of 2 and 3 bound to the active site of AChE for the competitive inhibitory activities, while the mixed inhibitory activity of 4 was due to the two binding patterns in the active‐site and the active‐site entrance of AChE. Furthermore, the docking studies indicated that 1, 5, and 6 would inhibit AChE in a mixed inhibitory manner by adopting three distinct binding patterns of the additional phenyl‐β‐D‐glucopyranoside unit at the active‐site entrance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Biologically active cannabinoids are derived from cannabigerolic acid (CBGA), which is biosynthesized by aromatic prenyltransferase CsPT4. We exploit the catalytic versatility of CsPT4 to synthesize ...various CBGA analogues, including a geranylated bibenzyl acid, the precursor to bibenzyl cannabinoids of liverwort origin. The synthesized natural and new-to-nature cannabinoids exhibit potent cytotoxicity in human pancreatic cancer cells. CsPT4 can artificially extend the cannabinoid biosynthetic diversity with novel and improved biological activities.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
A new fructofuranoside glycerol, dryoptkirbioside (
1
), along with thirteen known compounds (
2
‐
14
), was isolated from the MeOH extract of
Dryopteris kirbi
rhizomes by silica gel column ...chromatography, Sephadex LH‐20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high‐resolution electrospray ionisation mass spectrometry (HR‐ESI‐MS) and chemical conversions. The hexane‐soluble portion and the EAF
A
fraction showed strong activities against lung (A549), breast (MCF‐7), and cervical (HeLa) human cancer cell lines (IC
50
values ranging from 4.0 to 8.8 μg/mL). Aspidinol P (
5
) and aspidinol B (
6
) exhibited moderate to low cytotoxicity on the three cell lines (IC
50
values ranging from 20.4 to 58.7 μM). The MeOH extract and hexane‐soluble portion had excellent activities against
Staphylococcus aureus
and
Bacillus subtilis
(MICs 11.7 and 23.4 μg/mL), whereas the AcOEt‐ and BuOH‐soluble portions were significantly active on
S. aureus
(MICs 46.9 and 93.8 μg/mL). The main fractions EAF
B
, EAF
C
and nBF
B
displayed excellent activity against
S. aureus
(MICs 11.7 and 23.4 μg/mL). Aspidinol B (
6
) had significant activity, while aspidinol P (
5
) was moderately active against
S. aureus
and
B. subtilis
(MICs 42.0 and 89.5 μM).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Investigations of antibacterial activities revealed that the incorporation of longer alkyl chains to the C-6 position in resorcylic acid conferred antibacterial properties against
Staphylococcus ...aureus
and
Bacillus subtilis
. The resultant olivetolic acid (OA) derivatives with
n
-undecyl and
n
-tridecyl side-chains, even those lacking the hydrophobic geranyl moiety from their C-3 positions, exhibited strong antibacterial activities against
B. subtilis
at a MIC value of 2.5 μM. Furthermore, the study demonstrated that the
n
-heptyl alkyl-chain modification at C-6 of cannabigerolic acid (CBGA) effectively enhanced the activity against
B. subtilis
, demonstrating the importance of the alkyl side-chain in modulating the bioactivity. Overall, the findings in this study provided insight into further evaluations of the antibacterial activities, as well as other various biological activities of OA and CBGA derivatives, especially with optimized hydrophobicities at both the alkyl and prenyl side-chain positions of the core skeleton for the discovery of novel drug seeds.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis ...pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6′′-galloyl)-β-d-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Phytochemical investigation of Alsophila manniana rhizomes led to the isolation of twelve known compounds, including two triterpenes (1 and 2), four steroids (3–6), one glycerol (7), three phenols ...(8–10), and two flavonoids (11 and 12). Their structures were elucidated by analyses of the NMR and MS data and by comparisons with those in the literature. Their antibacterial and cytotoxic activities were evaluated against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus subtilis; and on human lung A549, cervical HeLa, and breast MCF-7 cancer cell lines, respectively. Fractions FD and FF had significant activities against E. coli (MIC = 75 μg/mL) and K. pneumoniae (MICs = 75 and 37.5 μg/mL). Compounds 3 and 7–12 had moderate antibacterial activities with MIC values ranging from 75 to 150 μg/mL against the bacteria. All samples were inactive against all tested human cancer cell lines, even at 100 μg/mL. This is the first investigation of the chemical constituents of A. manniana, as well as the first report of compounds 3, 7, and 10–12 from the genus Alsophila. The chemotaxonomic significance of these compounds is discussed.
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•First phytochemical investigation of a medicinal plant of Cameroon, Alsophilamanniana.•Twelve secondary metabolites identified by NMR, MS and literature.•Excellent antibacterial activity MIC 37.5 and 75 μg/mL by fractions FF and FD.•The chemotaxonomic significance of these compounds was discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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