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Lee, Jin ; Park, Hyun-Ah ; Shin, Kyung-Chul , et al. Bioresour. Technol.,2023,388,129750. DOI: 10.1016/j.biortech.2023.129750 PubMed ID: 37717704
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Abstract: Resolvin D5 (RvD5), 7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-docosahexaenoic acid (DHA) is a specialized pro-resolving mediator (SPM) generated in human macrophages. It is implicated in the resolution of inflammation and synthesized using an inefficient chem. process. Here, DHA-enriched oil hydrolyzate was prepared from oils by lipase with resin treatment and solvent extraction The reaction factors on the biotransformation of oil hydrolyzate into RvD5 were optimized using Escherichia coli expressing arachidonate double-oxygenating 15S-lipoxygenase. After optimization, the cells converted 5.0 mM (1.64 g/L) DHA in oil hydrolyzate into 4.0 mM (1.44 g/L) RvD5 in a bioreactor for 3.0 h, which was 15-fold higher than that in a flask before optimization, and RvD5 with a purity of > 97% was prepared from reaction solution by treatments of resins. This is the first trial for the production of C22-dihydroxy fatty acid using a bioreactor. This study will contribute to the large-scale production of SPMs from oils.
Keywords: Lipoxygenase ; Resolvin D5 ; Docosahexaenoic acid-enriched oil hydrolysate ; Biotransformation ; Bioreactor
Purchased from AmBeed: 10417-94-4 ; 6217-54-5 ; 506-32-1 ; 92693-03-3
CAS No. : | 6217-54-5 | MDL No. : | MFCD00065722 |
Formula : | C22H32O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 328.49 | Pubchem ID : | - |
Synonyms : |
DHA;Cervonic acid;Doconexent;C22:6 (all cis-4,7,10,13,16,19) omega-3 Fatty acid;Docosahexaenoic acid (all cis-4,7,10,13,16,19)
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P210-P261-P264-P271-P273-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501 | UN#: | N/A |
Hazard Statements: | H227-H315-H319-H335-H413 | Packing Group: | N/A |
GHS Pictogram: |
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* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triethylamine; HATU; In acetonitrile; at 0 - 20℃; | Example 21; Preparation of N-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidopropyl)-2-hydroxybenzamide (14); To a solution of tert-butyl 2-aminopropylcarbamate (1.06 g, 6.09 mmol, prepared as previously described), DHA (2.0 g, 6.09 mmol) and Et3N (1.7 mL, 12.8 mmol) in CH3CN (40 mL) at 0° C. was added HATU (2.31 g, 6.09 mmol). The mixture was stirred (RT, 16 h) and concentrated under reduced pressure. The residue was diluted with brine (100 mL) and extracted with EA (2.x.100 mL). The combined organic layers were washed with saturated NaHCO3 (100 mL) and brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel, eluting with EA-PE (0-25percent) to afford tert-butyl 2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidopropylcarbamate (2.1 g, 70percent) as a light yellow oil. Mass calculated for C30H48N2O3=484.71; found: [M+H]+=485.6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In acetonitrile; at 20℃; for 2h; | <strong>[263162-13-6]tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate</strong> (430 mg, 1.98 mmol) was taken up in 10 mL of CH3CN along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa- 4,7,10,13,16,19-hexaenoic acid (DHA, 650 mg, 1.98 mmol), HATU (750 mg, 2.2 mmol) and DIEA (0.550 mL). The resulting reaction mixture was stirred at room temperature for 2 h and then diluted with EtOAc (40 mL). The organic layer was washed with brine, dried (Na2S04) and concentrated under reduced pressure. Purification by chromatography (95% CH2C12, 5% MeOH) afforded 400 mg of the Boc-protected intermediate. This material was taken up in 3 mL of 4 M HC1 in dioxane and allowed to stir at room temperature for 10 min. The reaction mixture was concentrated under reduced pressure to afford the HCl salt of (4Z,7Z, 10Z, 13Z, 16Z, 19Z)-N-(2-((2-aminoethyl)(methyl)amino)ethyl)docosa- 4,7,10,13,16,19-hexaenamide. | |
With N-ethyl-N,N-diisopropylamine; HATU; at 20℃; for 2h; | <strong>[263162-13-6]tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate</strong> (430 mg, 1.98 mmol) was taken up in 10 mL of CH3CN along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19- hexaenoic acid (DHA, 650 mg, 1.98 mmol), HATU (750 mg, 2.2 mmol) and DIEA (0.550 mL). The resulting reaction mixture was stirred at room temperature for 2 h and then diluted with EtOAc (40 mL). The organic layer was washed with brine, dried (Na2S04) and concentrated under reduced pressure. Purification by chromatography (95% CH2CI2, 5% MeOH) afforded 400 mg of the Boc-protected intermediate. This material was taken up in 3 mL of 4 M HCl in dioxane and allowed to stir at room temperature for 10 min. |
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