An Improved Scalable Synthesis of α- and β-Amyrin

Serbian, Immo; Csuk, René

doi:10.3390/molecules23071552

Cited by 12 publications

(7 citation statements)

References 30 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ethanolic extract of E asperula (EEEA) was subjected to open column chromatography, isolating 10 known compounds ( 1 - 10 ). Comparison of the compounds’ physical and spectroscopic data (please see Supplemental file) with those reported in the literature identified the components as lithospermic acid B ( 1 ) 15 , ethyl lithospermate ( 2 ) 16 , clinopodic acid B ( 3 ) 17 , rosmarinic acid( 4 ) 18 , methyl rosmarinic acid ( 5 ) 18 , kaempferol 3-rutinoside ( 6 ) 19 , astragalin ( 7 ) 20 , caffeic acid ( 8 ) 21 , β-amyrin (9) 22 , and α -amyrin (10) 22 (Figure 1).…”

Section: Resultsmentioning

confidence: 86%

Protection Against Oxidative Stress-Induced Retinal Cell Death by Compounds Isolated From Ehretia asperula

Kang

Thi

et al. 2021

Natural Product Communications

View full text Add to dashboard Cite

Ehretia asperula ( E asperula) is a well-known traditional medicinal plant in Vietnam with potent activity against a wide range of diseases, including hepatitis B and various cancers. Although E asperula has been used in traditional medicine, the efficacy of E asperula and its bioactive components on retinal degenerative diseases has not been fully evaluated. In present this study, we found that ethanolic extracts of E asperula increased cell viability in retinal precursor cells exposed to glutamate/BSO-induced excitotoxicity/oxidative stress. The major responsible bioactive compounds were rosmarinic acid and methylrosmarinic acid. First, 10 known compounds were isolated from E asperula leaves. Their chemical structures were determined using 1D and 2D nuclear magnetic resonance, and compared with published data. Using high-performance liquid chromatography, we determined the content of 4 compounds in E asperula extract: rosmarinic acid, lithospermic acid B, astragalin, and kaempferol 3-rutinoside. The most abundant of these compounds was lithospermic acid B. The protective effects of the pure compounds and ethanolic extracts against excitotoxicity and oxidative stress-induced retinal cell death were tested in R28 cells. Both 70% and 95% ethanolic extracts of E asperula increased cell viability in these conditions. Rosmarinic acid and methyl rosmarinic acid were more effective at protecting against retinal cell death and elevated reactive oxygen species in cells subjected to glutamate/BSO-induced excitotoxicity/oxidative stress. These findings suggested that E asperula could potentially be used to treat retinal degeneration.

show abstract

Section: Resultsmentioning

confidence: 86%

Protection Against Oxidative Stress-Induced Retinal Cell Death by Compounds Isolated From Ehretia asperula

Kang

Thi

et al. 2021

Natural Product Communications

View full text Add to dashboard Cite

show abstract

“…To test whether our strategy can be widely applied to enhance the production of other terpenoids, we first established the synthesis of two other kinds of triterpenoids (α- and β-amyrin) by expressing α-amyrin synthetase from Malus domestica ( αAS ) and β-amyrin synthetase from A. thaliana ( βAS ), respectively [ 49 ] (Fig. 7 a).…”

Section: Resultsmentioning

confidence: 99%

High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components

Zhang

Bai

Peng

et al. 2020

Biotechnol Biofuels

View full text Add to dashboard Cite

Background: Lupeol exhibits novel physiological and pharmacological activities, such as anticancer and immunityenhancing activities. However, cytotoxicity remains a challenge for triterpenoid overproduction in microbial cell factories. As lipophilic and relatively small molecular compounds, triterpenes are generally secreted into the extracellular space. The effect of increasing triterpene efflux on the synthesis capacity remains unknown. Results: In this study, we developed a strategy to enhance triterpene efflux through manipulation of lipid components in Y. lipolytica by overexpressing the enzyme Δ9-fatty acid desaturase (OLE1) and disturbing phosphatidic acid phosphatase (PAH1) and diacylglycerol kinase (DGK1). By this strategy combined with two-phase fermentation, the highest lupeol production reported to date was achieved, where the titer in the organic phase reached 381.67 mg/L and the total production was 411.72 mg/L in shake flasks, exhibiting a 33.20-fold improvement over the initial strain. Lipid manipulation led to a twofold increase in the unsaturated fatty acid (UFA) content, up to 61-73%, and an exceptionally elongated cell morphology, which might have been caused by enhanced membrane phospholipid biosynthesis flux. Both phenotypes accelerated the export of toxic products to the extracellular space and ultimately stimulated the capacity for triterpenoid synthesis, which was proven by the 5.11-fold higher ratio of extra/intracellular lupeol concentrations, 2.79-fold higher biomass accumulation and 2.56-fold higher lupeol productivity per unit OD in the modified strains. This strategy was also highly efficient for the biosynthesis of other triterpenes and sesquiterpenes, including α-amyrin, β-amyrin, longifolene, longipinene and longicyclene. Conclusions: In conclusion, we successfully created a high-yield lupeol-producing strain via lipid manipulation. We demonstrated that the enhancement of lupeol efflux and synthesis capacity was induced by the increased UFA content and elongated cell morphology. Our study provides a novel strategy to promote the biosynthesis of valuable but toxic products in microbial cell factories.

show abstract

“…orbiculatus were isolated to yield six diterpenoids ( 1 – 6 ), nine triterpenoids ( 7 – 15 ), and two steroids ( 16 and 17 ) using various column chromatography. Their chemical structures were elucidated as (+)-7-deoxynimbidiol ( 1 ) [ 38 ], nimbidiol ( 2 ) [ 39 ], celaphanol A ( 4 ) [ 39 ], (+)-ferruginol ( 5 ) [ 40 ], dehydroabietic acid ( 6 ) [ 41 ], lupenone ( 7 ) [ 42 ], lupeol ( 8 ) [ 42 ], betulin ( 9 ) [ 43 ], 2 β ,3 β -dihydroxylup-20(29)-ene ( 10 ) [ 44 ], 3 β -caffeoyloxylup-20(29)-en-6 α -ol ( 11 ) [ 45 ], lup-20(29)-en-28-ol-3 β -yl caffeate ( 12 ) [ 43 ], dammarenediol II 3-caffeate ( 13 ) [ 46 ], β -amyrin ( 14 ) [ 47 ], α -amyrin ( 15 ) [ 47 ], sitostenon ( 16 ) [ 48 ], and ergone ( 17 ) [ 49 ], compared to previous reported spectroscopic data, NMR, MS, and optical rotation values. Among these, 13 compounds ( 3 , 5 – 13 , and 15 – 17 ) containing compound 3 determined as novel podocarpane trinorditerpenoid based on HRESIMS and NMR data were first reported from C .…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Activity of Diterpenoids fromCelastrus orbiculatusin Lipopolysaccharide-Stimulated RAW264.7 Cells

Jang

Kim

Park

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

Celastrus orbiculatus Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of C. orbiculatus extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds 1–17, including undescribed podocarpane-type trinorditerpenoid (3), were purified from C. orbiculatus and their chemical structure were determined by high-resolution electrospray ionization mass (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data. To investigate the anti-inflammatory activity of compounds 1–17, nitric oxide (NO) secretion was evaluated in LPS-treated murine macrophages, RAW264.7 cells. Among compounds 1–17, deoxynimbidiol (1) and new trinorditerpenoid (3) showed the most potent inhibitory effects (IC50: 4.9 and 12.6 μM, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α. Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) κB and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-κB (IκB), extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. Therefore, these results demonstrated that diterpenoids 1 and 3 obtained from C. orbiculatus may be considered a potential candidate for the treatment of inflammatory diseases.

show abstract

An Improved Scalable Synthesis of α- and β-Amyrin

Cited by 12 publications

References 30 publications

Protection Against Oxidative Stress-Induced Retinal Cell Death by Compounds Isolated From Ehretia asperula

Protection Against Oxidative Stress-Induced Retinal Cell Death by Compounds Isolated From Ehretia asperula

High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components

Anti-Inflammatory Activity of Diterpenoids fromCelastrus orbiculatusin Lipopolysaccharide-Stimulated RAW264.7 Cells

Contact Info

Product

Resources

About