Lipstatin
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| Category | Enzyme inhibitors |
| Catalog number | BBF-03784 |
| CAS | 96829-59-3 |
| Molecular Weight | 491.70 |
| Molecular Formula | C29H49NO5 |
| Purity | >95% |
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Description
Lipstatin, a potent inhibitor of the pancreas lipase, is reported to be useful in the treatment and prevention of obesity and related diseases. It is a natural product that was first isolated from Actinobacterium Streptomyces toxytricini.
Specification
| Synonyms | N-Formyl-L-leucine (1S,3Z,6Z)-1-[[(2S,3S)-3-Hexyl-4-oxo-2-oxetanyl]methyl]-3,6-dodecadien-1-yl Ester; N-Formyl-L-leucine [2S-[2α(1R*,3Z,6Z),3β]]-1-[(3-Hexyl-4-oxo-2-oxetanyl)methyl]-3,6-dodecadienyl Ester; (-)-Lipstatin |
| Storage | Store at -20°C |
| IUPAC Name | [(2S,4Z,7Z)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]trideca-4,7-dien-2-yl] (2S)-2-formamido-4-methylpentanoate |
| Canonical SMILES | CCCCCCC1C(OC1=O)CC(CC=CCC=CCCCCC)OC(=O)C(CC(C)C)NC=O |
| InChI | InChI=1S/C29H49NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h12-13,15-16,22-27H,5-11,14,17-21H2,1-4H3,(H,30,31)/b13-12-,16-15-/t24-,25-,26-,27-/m0/s1 |
| InChI Key | OQMAKWGYQLJJIA-CUOOPAIESA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Colorless to Yellow Thick Oil |
| Boiling Point | 627.4°C at 760 mmHg |
| Density | 0.993 g/cm3 |
| Solubility | Soluble in ethanol, methanol, DMF, DMSO |
Reference Reading
1. Development and Optimization of a High-Throughput Screening Assay for Rapid Evaluation of Lipstatin Production by Streptomyces Strains
Nora Rapavá, Michal Híreš, Svetlana Kryštofová, Martin Šimkovič, Dušan Berkeš, Ľudovít Varečka Curr Microbiol . 2018 May;75(5):580-587. doi: 10.1007/s00284-017-1420-x.
Pancreatic lipase inhibitors, such as tetrahydrolipstatin (orlistat), are used in anti-obesity treatments. Orlistat is the only anti-obesity drug approved by the European Medicines Agency (EMA). The drug is synthesized by saturation of lipstatin, a β-lactone compound, isolated from Streptomyces toxytricini and S. virginiae. To identify producers of novel pancreatic lipase inhibitors or microbial strains with improved lipstatin production and higher chemical purity remains still a priority. In this study, a high-throughput screening method to identify Streptomyces strains producing potent pancreatic lipase inhibitors was established. The assay was optimized and validated using S. toxytricini NRRL 15443 and its mutants. Strains grew in 24-well titer plates. Lipstatin levels were assessed directly in culture medium at the end of cultivation by monitoring lipolytic activity in the presence of a chromogenic substrate, 1,2-Di-O-lauryl-rac-glycero-3-glutaric acid 6-methylresorufin ester (DGGR). The lipase activity decreased in response to lipstatin production, and this was demonstrated by accumulation of red-purple methylresorufin, a product of DGGR digestion. The sensitivity of the assay was achieved by adding a lipase of high lipolytic activity and sensitivity to lipstatin to the reaction mixture. In the assay, the fungal lipase from Mucor javanicus was used as an alternative to the human pancreatic lipase. Many fungal lipases preserve high lipolytic activity in extreme conditions and are not colipase dependent. The assay proved to be reliable in differentiation of strains with high and low lipstatin productivity.
2. Modulation of fatty acid metabolism and tricarboxylic acid cycle to enhance the lipstatin production through medium engineering in Streptomyces toxytricini
Kashyap Kumar Dubey, Punit Kumar Bioresour Technol . 2016 Aug;213:64-68. doi: 10.1016/j.biortech.2016.01.133.
This work investigated the potential of medium engineering to obtain maximum biomass, non-conventional carbon sources for lipstatin production and modulation of tricarboxylic acid (TCA) cycle to promote lipstatin synthesis. It was found that 2:3 carbon and nitrogen ratio, produced maximum biomass of 7.9g/L in growth medium and 6.6g/L in pre-seed medium. Among the studied non-conventional carbon sources i.e., soya flour 40g/L and sesame oil 30mL/L were found producing 1109.37mg/L (1.24-fold of control) and 1196.75mg/L (1.34-fold of control) lipstatin respectively. Supplementation of TCA cycle intermediates revealed that NADH and succinic acid showed lipstatin production to 1132.99mg/L and 1171.10mg/L respectively. Experimental outcome was validated in 7L bioreactor and produced 2242.63mg/L lipstatin which was ~14% higher than shake flask.
3. Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity
E Kupfer, E Hochuli, P Hadvary, E K Weibel, H Lengsfeld J Antibiot (Tokyo) . 1987 Aug;40(8):1081-5. doi: 10.7164/antibiotics.40.1081.
Lipstatin, a new and very potent inhibitor of pancreatic lipase (the key enzyme of intestinal fat digestion) was isolated from Streptomyces toxytricini. Lipstatin contains a beta-lactone structure that probably accounts for the irreversible lipase inhibition. The IC50 of lipstatin for pancreatic lipase is 0.14 microM. In mice triolein absorption was dose-dependently inhibited by lipstatin, whereas oleic acid was absorbed normally. Other pancreatic enzymes, such as phospholipase A2 and trypsin, were not inhibited even at an inhibitor concentration of 200 microM.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
