Ultrasound-assisted solvent extraction of phenolics, flavonoids, and major triterpenoids from Centella asiatica leaves: A comparative study.

Centella asiatica has been known for its significant medicinal properties due to abundance of bioactive constituents like triterpenoids and flavonoids. Nevertheless, an appropriate solvent system and extraction technique is still lacking to ensure optimized extraction of bioactive constituents present in C. asiatica. Recently, scientists are more focused towards application of green sustainable extraction techniques for the valuable components from plant matrix owing to their eco-friendly and safe nature. Among these, ultrasonication (US) is known as a valuable strategy for separation of bioactive components from medicinal plants. Hence, current research was performed to observe the effect of ultrasonication in the presence of five different solvents (Water, Hexane, Methanol, Chloroform, and Ethyl acetate) on total phenolic contents (TPC), total flavonoid contents (TFC), antioxidant properties (DPPH, ABTS, Nitric oxide radical activity, and Superoxide anion assay), and four major triterpenoid contents in C. asiatica leaves. Herein, ultrasound assisted methanolic extract (UAME) possessed maximum amount of TPC (129.54 mg GAE/g), TFC (308.31 mg QE/g), and antioxidant properties (DPPH: 82.21 % & FRAP: 45.98 µmol TE/g) followed by ultrasound-assisted Water extract (UAWE), ultrasound-assisted ethyl acetate extract (UAEAE), ultrasound-assisted n-hexane extract (UAHE), and ultrasound-assisted chloroform extract (UACE), respectively. Moreover, the superoxide radical and nitric oxide assays depicted a similar trend, revealing the highest percent inhibition for UAME (SO: 83.47 % & NO: 66.76 %) however, the lowest inhibition was displayed by UACE (63.22 % & 50.21 %), respectively. Highest content of major terpenoids were found in UAME of C. asiatica leaves as madecassoside (8.21 mg/g) followed by asiaticoside (7.82 mg/g), madecassic acid (4.44 mg/g), and asiatic acid (3.38 mg/g). Ultrasound-assisted extraction technique can be an efficient extraction method for bioactive compounds present in C. asiatica. However, ultrasonication along with methanol as an extraction solvent can surely enhance the extraction of valuable constituents. The results of this study provide an insight into major terpenoids, and antioxidants present in extracts of C. asiatica, implicating its use in ancient medicine systems and future drug development.

Antiradical effect and phytochemical characterisation of the leaves of Parkia platycephala Benth.

The objective of this study was to isolate and identify compounds present in the leaves of Parkia platycephala Benth (Leguminosae-Mimosoideae) and evaluate the antiradical potential of the derived extracts and fractions. Seven compounds were successfully isolated from the ethanolic leaf extract, comprising gallic acid, flavonoids, triterpenoids, and phytosteroids. Structural identification was accomplished through comprehensive spectroscopic data analysis, including NMR and mass spectrometry (ESI-MS), and comparison with existing literature. The antiradical efficacy of both the extract and its fractions was determined in vitro through assays measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and quantifying total phenolics via UV/Vis, revealing notable antioxidant activity in extracts from P. platycephala Benth, especially in the EtOH, EtOAc, and aqueous fractions, attributed to their high phenolic content and prevalence of flavonoids. These findings contribute to a deeper understanding of Parkia's chemical composition and its potential biological benefits.

Structure-Agnostic Bioactivity-Driven Combinatorial Biosynthesis Reveals New Antidiabetic and Anticancer Triterpenoids.

Although combinatorial biosynthesis can dramatically expand the chemical structures of bioactive natural products to identify molecules with improved characteristics, progress in this direction has been hampered by the difficulty in isolating and characterizing the numerous produced compounds. This challenge could be overcome with improved designs that enable the analysis of the bioactivity of the produced metabolites ahead of the time-consuming isolation procedures. Herein, we showcase a structure-agnostic bioactivity-driven combinatorial biosynthesis workflow that introduces bioactivity assessment as a selection-driving force to guide iterative combinatorial biosynthesis rounds towards enzyme combinations with increasing bioactivity. We apply this approach to produce triterpenoids with potent bioactivity against PTP1B, a promising molecular target for diabetes and cancer treatment. We demonstrate that the bioactivity-guided workflow can expedite the combinatorial process by enabling the narrowing down of more than 1000 possible combinations to only five highly potent candidates. By focusing the isolation and structural elucidation effort on only these five strains, we reveal 20 structurally diverse triterpenoids, including four new compounds and a novel triterpenoid-anthranilic acid hybrid, as potent PTP1B inhibitors. This workflow expedites hit identification by combinatorial biosynthesis and is applicable to many other types of bioactive natural products, therefore providing a strategy for accelerated drug discovery.

A Novel Dipterocarpol Derivative that Targets Alpha-Glucosidase and NLRP3 Inflammasome Activity for Treatment of Diabetes Mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia, chronic inflammation, impaired insulin secretion, and/or peripheral insulin resistance. Current α-glucosidase inhibitors approved for clinical use exhibit limited efficacy compared to other glucose-lowering agents. In this study, a series of mono- and bis-benzylidene derivatives were synthesized via aldol condensation of 3-oxo-dammarane triterpenoids with terephthalic aldehyde. The target mono- and bis-benzylidene derivatives, based on the dammarane triterpenoids hollongdione 1, (20S)-23,24-epoxy-25,26,27-trinordammar-3,24-dione 2, and 24(R,S)-20(S)-epoxy-25-hydroxy-dammar-3-one 3, were successfully synthesized. Several of these inhibitors demonstrated significantly greater efficacy than the reference drug acarbose. Notably, compound 4 inhibited S. cerevisiae α-glucosidase with an IC50 of 2.67 µM. Furthermore, the target compounds effectively inhibited NLRP3 inflammasome activation, reducing IL-1ß production in LPS+ATP-stimulated murine peritoneal macrophages without detectable cytotoxicity. Compound 8, which exhibited dual activity, was further characterized as an inhibitor of NLRP3 activation in peripheral blood mononuclear cells, leading to the prevention of pyroptosis and IL-1ß release. Additionally, compound 8 was shown to promote neuronal survival in LPS+ATP-treated rat hippocampal slices, highlighting its potential as a promising antidiabetic agent that targets both postprandial hyperglycemia and metaflammation.

Physical radiation induced the yield of triterpenoids in hypha of Inonotus obliquus to increase.

HSD-IO01, a new pure strain of I. obliquus, was isolated and purified from the sclerotium of I. obliquus of Daxing'an Mountains. Physical radiation-assisted liquid fermentation technology was explored to increase the triterpenoids yield of HSD-IO01. In the 100 mL optimized liquid fermentation system, the hypha dry weight of HSD-IO01 was 1.7734 g, and the triterpenoids yield was 43.43 mg. Yields of triterpenoids increased after induction with ultrasound, microwave, or UV light, respectively. Among them, ultrasonic treatment had the most remarkable induction effect. The yield of triterpenoids would be increased to 68.35 mg (57.38 %) when the HSD-IO01 was treated by 100 W ultrasonic for 45 min. Establishing ultrasonic-assisted liquid fermentation technology could further promote the detailed development and comprehensive utilization of I. obliquus resources.

Efficient enrichment and characterization of triterpenoid saponins from Platycodon grandiflorus roots.

Platycodon grandiflorum roots (PGR), a widely recognized edible herbal medicine, are extensively used in traditional Chinese medicine for respiratory ailments. PGR are rich in bioactive compounds, particularly triterpenoid saponins, which possess significant pharmaceutical properties, including anti-inflammatory, antifungal, and antioxidant activities. Despite their recognized bioactivity, the purification and enrichment processes of triterpenoid saponins remain underexplored. This study aimed to optimize the extraction and purification of triterpenoid saponins from PGR to enhance resource utilization and minimize waste. Our method involved n-butanol extraction and macroporous adsorption resin, yielding four extracts with varying saponins contents. Qualitative analysis using LC-MS identified 8 triterpenoid saponins across the extracts. Further fragmentation analysis delineated characteristic ion patterns and cleavage pathways for these compounds. Quantitative analysis demonstrated that the separation and purification process effectively increased the triterpenoid saponins content, with the highest levels obtained through 30 % ethanol elution. Notably, the absence of Platycodin D in the 30 % ethanol eluate highlighted potential variations due to the origin, processing, and purification methods. These findings provide theoretical support for the development and utilization of triterpenoid saponins in PGR.

Effects of Inonotus obliquus on ameliorating podocyte injury in ORG mice through TNF pathway and prediction of active compounds.

Background: Podocyte injury is a common pathologic mechanism in diabetic kidney disease (DKD) and obesity-related glomerulopathy (ORG). Our previous study confirmed that Inonotus obliquus (IO) improved podocyte injury on DKD rats. The current study explored the pharmacological effects, related mechanisms and possible active components of IO on ORG mice. Methods: Firstly, by combining ultra-high performance liquid chromatography tandem mass spectrometry analysis (UPLC-Q-TOF-MS) with network pharmacology to construct the human protein-protein interaction mechanism and enrich the pathway, which led to discover the crucial mechanism of IO against ORG. Then, ORG mice were established by high-fat diet and biochemical assays, histopathology, and Western blot were used to explore the effects of IO on obesity and podocyte injury. Finally, network pharmacology-based findings were confirmed by immunohistochemistry. The compositions of IO absorbed in mice plasma were analyzed by UPLC-Q-TOF-MS and molecular docking was used to predict the possible active compounds. Results: The network pharmacology result suggested that IO alleviated the inflammatory response of ORG by modulating TNF signal. The 20-week in vivo experiment confirmed that IO improved glomerular hypertrophy, podocyte injury under electron microscopy, renal nephrin, synaptopodin, TNF-α and IL-6 expressions with Western blotting and immunohistochemical staining. Other indicators of ORG such as body weight, kidney weight, serum total cholesterol, liver triglyceride also improved by IO intervention. The components analysis showed that triterpenoids, including inoterpene F and trametenolic acid, might be the pharmacodynamic basis. Conclusion: The research based on UPLC-Q-TOF-MS analysis, network pharmacology and in vivo experiment suggested that the amelioration of IO on podocyte injury in ORG mice via its modulation on TNF signal. Triterpenoids were predicated as acting components.

Establishing cell suitability for high-level production of licorice triterpenoids in yeast.

Yeast has been an indispensable host for synthesizing complex plant-derived natural compounds, yet the yields remained largely constrained. This limitation mainly arises from overlooking the importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein, beyond conventional enzyme engineering, we dissected metabolic suitability with a framework for simultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenous triterpenoids. We further developed phospholipid microenvironment engineering strategies, dramatically improving yeast's suitability for the high performance of endoplasmic reticulum (ER)-localized, rate-limiting plant P450s. Combining metabolic and microenvironment suitability by manipulating only three genes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)and GPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rare licorice triterpenoids derived from consecutive oxidation of ß-amyrin by two P450 enzymes after fermentation optimization. This production holds substantial commercial value, highlighting the critical role of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatile framework applicable to various plant natural product biosynthetic pathways.

Simultaneous determination of cucurbitacins B, D, and E in Cucurbita seed oils by HPLC-DAD.

Cucurbitacins are triterpene bioactive constituents of natural products, particularly in the Cucurbitaceae plant family. The presence of cucurbitacins in seeds of the Cucurbita genus (pumpkin) has been only little studied. In this work, the content of cucurbitacins B, D, and E in seed oils from three cucurbits (Cucurbita moschata Duch, Cucurbita pepo Linn, and Cucurbita maxima Linn) was studied. An analytical method based on HPLC-DAD for the detection and quantification of these three cucurbitacins in seed oils was developed and validated according to ICH guidelines. The method showed good linearity, accuracy, and precision for the simultaneous quantification of cucurbitacins B, D, and E using C.moschata seed oil as a reference. When applied to C.pepo and C.maxima seed oils, cucurbitacin B and D were quantified but to a lesser extent. This is the first report of a simple, repeatable, and reproducible analytical tool to identify cucurbitacins in oilseeds from Cucurbita spp.

Assessment of the Lipophilicity of Indole Derivatives of Betulin and Their Toxicity in a Zebrafish Model.

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logPTLC) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logPTLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds.

A systematic review of spirostanol saponins and anticancer natural products isolated from Tacca plantaginea (Hance) Drenth.

The plant genus Tacca comprises twenty species including Tacca plantaginea, essentially distributed in the Indo-China region. Medicinal preparations from the rhizomes are used traditionally to treat gastrointestinal ailments, stomach aches and inflammatory disorders. A variety of bioactive molecules have been isolated from T. plantaginea, including potent anticancer steroids such as the taccanolides which interfere with microtubules dynamic. Other efficient anticancer natural products have been isolated from the plant, in particular a series of diosgenin/yamogenin-type sapogenins including taccaoside (monodesmosidic) and taccaoside A (bidesmosidic). Taccaoside A displays marked anticancer properties through two complementary mechanisms: a direct action on cancer stem cells via HRas and Pi3K/Akt signaling and an indirect immunomodulatory action via activation of cytotoxic T cells. A similar mechanism of action has been invoked with a total saponin extract from Schizocapsa plantaginea Hance (synonym to T. plantaginea) and the saponin SSPH 1. This saponin reduced tumor growth in mice through stimulation of cytotoxic T lymphocytes. Other bioactive products have been isolated from T. plantaginea, including withanolide-type steroids (plantagiolides, chantriolides), diarylheptanoids (plantagineosides) and different saponins (diosbulbisides, lieguonins). The discussion centers around the mechanism of action of spirostanol saponins, with the objective to promote their study as immuno-active anticancer agents.

Ursolic acid-based 24-nor- and A-seco-24-oxy-triterpenoids.

Using methyl 2-cyano-3,4-seco-12(13),4(23)-diene-ursolate as a starting scaffold a series of 3-oxo-24-nor-ursolate and A-seco-ursanes holding hydroxy-, furoyloxy-, p-tosyloxy- as well as aldehyde fragments at C24 that possess cytotoxic activity has been synthesised. The structures of the new ursanes were confirmed by detailed spectral data analysis. The chemoselectivity of methyl 2-cyano-3,4-seco-12(13),4(23)-diene-ursolate oxidation involving the double bond in the A cycle was observed.

Biological Properties, Health Benefits and Semisynthetic Derivatives of Edible Astraeus Mushrooms (Diplocystidiaceae): A Comprehensive Review.

Edible Astraeus mushrooms are known for their nutritional and culinary benefits and potential therapeutic properties. However, more investigation and discussion are still needed to understand their mechanisms of action regarding observed biological activities and thorough chemical analysis of bioactive compounds. This review provides a comprehensive summary and discussion of the bioactive properties and mode of action of Astraeus extracts and their isolated compounds. It covers their reported antioxidant, anti-inflammatory, antidiabetic, anticancer, anti-tuberculosis, antimalarial, antiviral and antileishmanial activities, as well as their potential benefits on metabolic and cardiovascular health and immune function. The review highlights the significance of the biological potential of isolated compounds, such as sugar alcohols, polysaccharides, steroids, and lanostane triterpenoids. Moreover, the review identifies under-researched areas, such as the chemical analysis of Astraeus species, which holds immense research potential. Ultimately, the review aims to inspire further research on the nutraceuticals or therapeutics of these mushrooms.

Potential Pharmacological Properties of Triterpene Derivatives of Ursolic Acid.

Ursolic acid (UA) and its derivatives have garnered significant attention due to their extensive pharmacological activity. UA is a pentacyclic triterpenoid found in a variety of plants, such as apples, rosemary, thyme, etc., and it possesses a range of pharmacological properties. Researchers have synthesized various derivatives of UA through structural modifications to enhance its potential pharmacological properties. Various in vitro and in vivo studies have indicated that UA and its derivatives possess diverse biological activities, such as anticancer, antifungal, antidiabetic, antioxidant, antibacterial, anti-inflammatory and antiviral properties. This review article provides a review of the biological activities of UA and its derivatives to show their valuable therapeutic properties useful in the treatment of different diseases, mainly focusing on the relevant structure-activity relationships (SARs), the underlying molecular targets/pathways, and modes of action.

Effect of a Triterpenoid-Rich Olive Oil on Chronic Kidney Disease in an Experimental Model of Diabetes Mellitus.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.

Chemical Content and Cytotoxic Activity on Various Cancer Cell Lines of Chaga (Inonotus obliquus) Growing on Betula pendula and Betula pubescens.

Chaga mushroom (Inonotus obliquus) is a pathogenic fungus that grows mostly on birch species (Betula pendula Roth and B. pubescens Ehrh.) and has traditionally been used as an anticancer medicine. This study aimed to compare the chemical composition and cytotoxic activity of chagas growing on both Betula spp. on various cancer cell lines. The freeze-dried extracts contained triterpenes inotodiol, lanosterol betulin, and betulinic acid typical to conks growing on Betula species. The cytotoxic activity of chaga growing on Betula pendula and B. pubescens 80% ethanolic extracts against 31 human cancer cell lines was evaluated by a sulforhodamine B assay. Chaga extract showed moderate activity against all cancer cell lines examined; it did not result in high cytotoxicity (IC50 ≤ 20 µg/mL). The strongest inhibitions were observed with chaga (growing on B. pendula) extract on the HepG2 and CAL-62 cell line and with chaga (from B. pubescens) extract on the HepG2 cell line, with IC50 values of 37.71, 43.30, and 49.99 µg/mL, respectively. The chaga extracts from B. pendula exert somewhat stronger effects on most cancer cell lines studied than B. pubescens extracts, which can be attributed to a higher content of inotodiol in B. pendula extracts. This study highlights the potential of chaga as a source of bioactive compounds with selective anticancer properties. To the best of our knowledge, this study is the first investigation of the chemical composition of I. obliquus parasitizing on B. pubescens.

Explore the mechanisms of triterpenoids from Ganoderma lucidum in the protection against Alzheimer's disease via microbiota-gut-brain axis with the aid of network pharmacology.

Ganoderma lucidum (Curtis) P. Karst.(G. lucidum) is a kind of fungi, which also a traditional Chinese medicine used for "wisdom growth" in China. Triterpenoids from G. lucidum (GLTs) are one of the main active ingredients. Based on the strategy of early intervention on Alzheimer's disease (AD) and the inextricable association between disordered gut microbiota and metabolites with AD, this study aimed to explore the mechanisms of GLTs in the protection against AD via microbiota-gut-brain axis with the aid of network pharmacology. In this study, LC-MS/MS was used to identify the main active ingredients of GLTs. Network pharmacology was used to predict the potential target and validated with Caco-2 cell model. D-galactose was used to induce the slow-onset AD on rats. Metabolomics methods basing on GC-MS combined with 16S rRNA sequencing technology was used to carry out microbiota-gut-metabolomics analysis in order to reveal the potential mechanisms of GLTs in the protection of AD. As results, GLTs showed a protection against AD effect on rats by intervening administration. The mechanisms were inextricably linked to GLTs interference with the balance of gut microbiota and metabolites. The main fecal metabolites involved were short-chain fatty acids and aromatic amino acid metabolites.

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Nine new nor-3,4-seco-dammarane triterpenoids from the leaves of Cyclocarya paliurus and their hypoglycemic activity.

This manuscript describes the isolation of nine new nor-3,4-seco-dammarane triterpenoids, norqingqianliusus A-I (1-9) and one known nortriterpenoid (10) from Cyclocarya paliurus leaves. Norqingqianliusus A and B (1 and 2) possess a unique 3,4-seco-dammarane-type C26 tetranortriterpenoid skeleton. The compounds were structurally characterized through modern spectroscopic techniques. Moreover, the potential mechanism of hypoglycemic activity was further explored by studying the effects on glucosamine-induced insulin resistant HepG2 cells. In vitro hypoglycemic effects of all of the isolates were investigated using insulin resistant HepG2 cells. The glucose consumption was significantly promoted by compound 10, in a dose-dependent manner, thus alleviating damage in IR-HepG2 cells. Besides, it reduced the PEPCK and GSK3ß gene expression, involved in glucose metabolism. The anti-diabetic effects of the plant, utilized traditionally, can hence be attributed to the presence of nor-3,4-seco-dammarane triterpenoids in the leaves.

Cultivation optimization promotes ginsenoside and universal triterpenoid production by engineered yeast.

Ginseng, a cornerstone of traditional herbal medicine in Asia, garnered significant attention for its therapeutic potential. Central to its pharmacological effects are ginsenosides, the primary active metabolites, many of which fall within the dammarane-type and share protopanaxadiol as a common precursor. Challenges in extracting protopanaxadiol and ginsenosides from ginseng arise due to their low concentrations in the roots. Emerging solutions involve leveraging microbial cell factories employing genetically engineered yeasts. Here, we optimized the fermentation conditions via the Design of Experiment, realizing 1.2 g/L protopanaxadiol in simple shake flask cultivations. Extrapolating the optimized setup to complex ginsenosides, like compound K, achieved 7.3-fold (0.22 g/L) titer improvements. Our adaptable fermentation conditions enable the production of high-value products, such as sustainable triterpenoids synthesis. Through synthetic biology, microbial engineering, and formulation studies, we pave the way for a scalable and sustainable production of bioactive compounds from ginseng.