Olivetolic Acid
(Synonyms: 2,4-二羟基-6-戊基苯甲酸,Olivetolate, Olivetolcarboxylic Acid) 目录号 : GC41526
An Analytical Reference Standard
Cas No.:491-72-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Olivetolic acid is an analytical reference standard categorized as an intermediate in the phytocannabinoid biosynthetic pathway. It is a precursor in the synthesis of cannabigerolic acid , δ9-tetrahydrocannabinol , and cannabidiol . This product is intended for research and forensic applications.
橄榄酸是一种分析参考标准，属于植物大麻素生物合成途径中的中间体。它是合成大麻酸、δ9-四氢大麻酚和大麻二酚的前体。该产品仅供研究和法医应用。
Reference:
[1]. Gagne, S.J., Stout, J.M., Liu, E., et al. Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc. Nat. Acad. Sci. USA 109(31), 12811-12816 (2012)..
| Cas No. | 491-72-5 | SDF | |
| 别名 | 2,4-二羟基-6-戊基苯甲酸,Olivetolate, Olivetolcarboxylic Acid | ||
| 化学名 | 2,4-dihydroxy-6-pentyl-benzoic acid | ||
| Canonical SMILES | OC1=CC(O)=C(C(O)=O)C(CCCCC)=C1 | ||
| 分子式 | C12H16O4 | 分子量 | 224.3 |
| 溶解度 | 50mg/mL in DMSO, 50mg/mL in DMF, 50mg/mL in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.4583 mL | 22.2916 mL | 44.5831 mL |
| 5 mM | 0.8917 mL | 4.4583 mL | 8.9166 mL |
| 10 mM | 0.4458 mL | 2.2292 mL | 4.4583 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Olivetolic Acid, a cannabinoid precursor in Cannabis sativa, but not CBGA methyl ester exhibits a modest anticonvulsant effect in a mouse model of Dravet syndrome
J Cannabis Res 2022 Jan 4;4(1):2.PMID:34980287DOI:10.1186/s42238-021-00113-w.
Objective: Cannabigerolic acid (CBGA), a precursor cannabinoid in Cannabis sativa, has recently been found to have anticonvulsant properties in the Scn1a+/- mouse model of Dravet syndrome. Poor brain penetration and chemical instability of CBGA limits its potential as an anticonvulsant therapy. Here, we examined whether CBGA methyl ester, a more stable analogue of CBGA, might have superior pharmacokinetic and anticonvulsant properties. In addition, we examined whether Olivetolic Acid, the biosynthetic precursor to CBGA with a truncated (des-geranyl) form, might possess minimum structural requirements for anticonvulsant activity. We also examined whether Olivetolic Acid and CBGA methyl ester retain activity at the epilepsy-relevant drug targets of CBGA: G-protein-coupled receptor 55 (GPR55) and T-type calcium channels. Methods: The brain and plasma pharmacokinetic profiles of CBGA methyl ester and Olivetolic Acid were examined following 10 mg/kg intraperitoneal (i.p.) administration in mice (n = 4). The anticonvulsant potential of each was examined in male and female Scn1a+/- mice (n = 17-19) against hyperthermia-induced seizures (10-100 mg/kg, i.p.). CBGA methyl ester and Olivetolic Acid were also screened in vitro against T-type calcium channels and GPR55 using intracellular calcium and ERK phosphorylation assays, respectively. Results: CBGA methyl ester exhibited relatively limited brain penetration (13%), although somewhat superior to that of 2% for CBGA. No anticonvulsant effects were observed against thermally induced seizures in Scn1a+/- mice. Olivetolic Acid also showed poor brain penetration (1%) but had a modest anticonvulsant effect in Scn1a+/- mice increasing the thermally induced seizure temperature threshold by approximately 0.4°C at a dose of 100 mg/kg. Neither CBGA methyl ester nor Olivetolic Acid displayed pharmacological activity at GPR55 or T-type calcium channels. Conclusions: Olivetolic Acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a+/- mouse model of Dravet syndrome despite poor brain penetration. The effect was, however, comparable to the known anticonvulsant cannabinoid cannabidiol in this model. Future studies could explore the anticonvulsant mechanism(s) of action of Olivetolic Acid and examine whether its anticonvulsant effect extends to other seizure types.
Biosynthesis of cannabinoid precursor Olivetolic Acid in genetically engineered Yarrowia lipolytica
Commun Biol 2022 Nov 12;5(1):1239.PMID:36371560DOI:10.1038/s42003-022-04202-1.
Engineering microbes to produce plant-derived natural products provides an alternate solution to obtain bioactive products. Here we report a systematic approach to sequentially identify the rate-limiting steps and improve the biosynthesis of the cannabinoid precursor Olivetolic Acid (OLA) in Yarrowia lipolytica. We find that Pseudomonas sp LvaE encoding a short-chain acyl-CoA synthetase can efficiently convert hexanoic acid to hexanoyl-CoA. The co-expression of the acetyl-CoA carboxylase, the pyruvate dehydrogenase bypass, the NADPH-generating malic enzyme, as well as the activation of peroxisomal β-oxidation pathway and ATP export pathway are effective strategies to redirect carbon flux toward OLA synthesis. Implementation of these strategies led to an 83-fold increase in OLA titer, reaching 9.18 mg/L of OLA in shake flask culture. This work may serve as a baseline for engineering cannabinoids biosynthesis in oleaginous yeast species.
Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs
Org Lett 2022 Jan 14;24(1):410-414.PMID:34939812DOI:10.1021/acs.orglett.1c04089.
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.
High-Titer Production of Olivetolic Acid and Analogs in Engineered Fungal Host Using a Nonplant Biosynthetic Pathway
ACS Synth Biol 2021 Sep 17;10(9):2159-2166.PMID:34415146DOI:10.1021/acssynbio.1c00309.
The microbial synthesis of cannabinoids and related molecules requires access to the intermediate Olivetolic Acid (OA). Whereas plant enzymes have been explored for E. coli and yeast biosynthesis, moderate yields and shunt product formation are major hurdles. Here, based on the chemical logic to form 2,4-dihydroxybenzoate-containing natural products, we discovered a set of fungal tandem polyketide synthases that can produce OA and the related octanoyl-primed derivative sphaerophorolcarboxylic acid in high titers using the model organism Aspergillus nidulans. This new set of enzymes will enable new synthetic biology strategies to access microbial cannabinoids.
Scale-up of an amoeba-based process for the production of the cannabinoid precursor Olivetolic Acid
Microb Cell Fact 2022 Oct 20;21(1):217.PMID:36266656DOI:10.1186/s12934-022-01943-w.
Background: The availability of new biological platform organisms to get access to innovative products and processes is fundamental for the progress in biotechnology and bioeconomy. The amoeba Dictyostelium discoideum represents a novel host system that has recently been employed for both the discovery of new natural products and as a cell factory for the production of bioactive compounds such as phytochemicals. However, an essential parameter to evaluate the potential of a new host system is the demonstration of its scalability to allow industrial applicability. Here, we aimed to develop a bioprocess for the production of Olivetolic Acid, the main precursor of cannabinoids synthesized by a recently engineered D. discoideum strain. Results: In this study, a sophisticated approach is described to scale-up an amoeba-based polyketide production process in stirred tank bioreactors. Due to the shear sensitivity of the cell wall lacking amoebae, the maximum local energy dissipation rate (εmax) was selected as a measure for the hydromechanical stress level among different scales. By performing 1.6-L scale batch fermentations with different stress conditions, we determined a maximum tolerable εmax of 3.9 W/kg for D. discoideum. Further, we used this parameter as scale-up criterion to develop a bioprocess for Olivetolic Acid production starting from a 7-L stirred tank reactor to the industrially relevant 300-L scale with a product concentration of 4.8 µg/L, a productivity of 0.04 µg/L/h and a yield of 0.56 µg/g glucose. Conclusion: We developed a robust and reliable scale-up strategy for amoeba-based bioprocesses and evaluated its applicability for the production of the cannabinoid precursor Olivetolic Acid. By determining the maximum tolerable hydromechanical stress level for D. discoideum, we were able to scale-up the process from shake flasks to the 300-L stirred tank reactor without any yield reduction from cell shearing. Hence, we showed the scalability and biotechnological exploitation of amoeba-based processes that can provide a reasonable alternative to chemical syntheses or extractions of phytochemicals from plant biomass.