CN103103222A - Method for producing R-alpha-hydroxybutyrate by using 1, 2-butanediol as substrate - Google Patents
Method for producing R-alpha-hydroxybutyrate by using 1, 2-butanediol as substrate Download PDFInfo
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- CN103103222A CN103103222A CN2011103551712A CN201110355171A CN103103222A CN 103103222 A CN103103222 A CN 103103222A CN 2011103551712 A CN2011103551712 A CN 2011103551712A CN 201110355171 A CN201110355171 A CN 201110355171A CN 103103222 A CN103103222 A CN 103103222A
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Abstract
The invention discloses a method for producing 1,2-butanediol by using R-alpha-hydroxybutyrate as a substrate. The method comprises steps of: culturing Gluconobacter oxydans DSM 2003 by a conventional method to prepare a biological catalyst; mixing the biological catalyst with a substrate 1,2-butylene glycol aqueous solution; adding ethylene diamine tetraacetic acid and oscillating for 1-30 h under condition of 20-50 DEG C and pH of 4.0-10.0 to obtain a transformation liquid; and preparing a solution containing R-alpha-hydroxybutyrate through the transformation liquid. The method provided by the invention has the following characteristics: (1) the method employs biological catalysis, has simple reaction system, mild reaction conditions, short steps and simple operation; and the biological catalyst can be easily removed, so as to facilitate subsequent separation and purification; (2) the method has a short reaction period, and the product R-alpha-hydroxybutyrate can accumulate to a high concentration; (3) the substrate 1,2-butanediol has low price, and is easy to acquire; and (4) product enantiomer has high excessive rate reaching higher than 99%, so as to lay foundation for the efficient production of R-alpha-hydroxybutyrate.
Description
Technical field
The present invention relates to a kind of method of the R-of production alpha-hydroxybutyric acid, specifically, relate to a kind of intact cell that utilizes bacillus of oxidizing glucose DSM 2003 as biological catalyst catalysis 1, the 2-butyleneglycol is produced the method for R-alpha-hydroxybutyric acid.
Background technology
Alpha-hydroxybutyric acid is a kind of important Industrial intermediates, can be used for synthesizing Isoleucine and some drugs.Alpha-hydroxybutyric acid is divided into R and two kinds of configurations of S.High-purity chiral R-alpha-hydroxybutyric acid can be used for the poly-alpha-hydroxybutyric acid [P (2HB)] of superpolymer of synthesizing biological degradable
[1]In addition, the R-alpha-hydroxybutyric acid can be used to prepare azinothricin family antitumor antibiotic
[2,3]
Through literature search, the initial substrate that is used for the production of high purity R-alpha-hydroxybutyric acid has two kinds usually.A kind of is α-alpha-ketobutyric acid, generates the R-alpha-hydroxybutyric acid by stereoselective enzyme reduction
[4]Another kind is the racemize alpha-hydroxybutyric acid, passes through acetylization reaction
[5]Perhaps oxidizing reaction
[6,7]Stereospecificity splits, and obtains high purity R-alpha-hydroxybutyric acid.No matter be α-alpha-ketobutyric acid or racemize alpha-hydroxybutyric acid, its price is all comparatively expensive and be difficult to obtain.Given this, in a large amount of productions of R-alpha-hydroxybutyric acid in the urgent need to selecting a kind of suitable and cheap initial substrate.
1,2-butyleneglycol has 1 and 2 hydroxyls, and 1 hydroxyl oxidize is that carboxyl can produce alpha-hydroxybutyric acid, thereby 1,2-butyleneglycol can be used as the potential substrate that the R-alpha-hydroxybutyric acid is produced; Bacillus of oxidizing glucose DSM 2003 can imperfection stereoselectivity oxidation carbohydrate, alcohols and acids
[8], thereby it might catalysis 1, the 2-butyleneglycol is produced the R-alpha-hydroxybutyric acid.Yet present result for retrieval shows: the method for utilizing bacillus of oxidizing glucose to produce the R-alpha-hydroxybutyric acid has no report.
Reference:
【1】Tsuji，H.，Okumura，A.，2009.Stereocomplex?formation?between?enantiomeric?substituted?poly(lactide)s：blends?of?poly[(S)-2-hydroxybutyrae]and?poly[(R)-2-hydroxybutyrate].Macromolecules?42，7263-7266.
【2】Karl，J.，Jia，C.，Soraya，M.，Andrew，P.，1995.Synthetic?studies?on?the?azinothricin?family?of?antibiotics.4.enantioselective?synthesis?of?the?northern?half?of?antitumour?antibiotics?A83586C?and?citropeptm.Tetrahedron?Lett.36，6965-6968.
【3】Nakagawa，A.，Kato，K.，Shinmyo，A.，Suzuki，T.，2007.Asymmetric?hydrolysis?of2-hydroxy-carboxylic?esters?using?recombinant?Escherichia?coli.Tetrahedron：Asymmetry?18，2394-2398.
【4】Simon，E.S.，Plante，R.，Whitesides，G.M.，1989.D-lactate?dehydrogenase.Substrate?specificity?and?use?as?a?catalyst?in?the?synthesis?of?homochiral?2-hydroxy?acids.Appl?Biochem?Biotechnol?22，169-179.
【5】Adam，W.，Lazarus，M.，Schmerder，A.，Humpf，H-U.，
C.R.，Schreier，P.，1998.Synthesis?of?optically?active?α-hydroxy?acids?by?kinetic?resolution?through?lipase-catalyzed?enantioselective?acetylation.Eur?J?Org?Chem?9，2013-2018.
【6】Adam，W.，Lazarus，M.，Saha-Moller，C.R.，Schreier，P.，1998.Quantitative?transformation?of?racemic2-hydroxy?acids?mto(R)-2-hydroxy?acids?by?enantioselective?oxidation?with?glycolate?oxidase?and?subsequent?reduction?of?2-keto?acids?with?D-lactate?dehydrogenase.Tetrahedron：Asymmetry?9，351-355.
【7】Gao，C.，Zhang，W.，Ma，C.，Liu，P.，Xu，P.，2011.Kinetic?resolution?of?2-hydroxybutanoate?racemicmixtures?by?NAD-independent?l-lactate?dehydrogenase.Bioresour?Technol?102，4595-4599.
Summary of the invention
For the deficiencies in the prior art, the problem to be solved in the present invention is to provide a kind of with 1, the 2-butyleneglycol is the method that substrate is produced the R-alpha-hydroxybutyric acid, to overcome substrate racemize alpha-hydroxybutyric acid in the preparation of R-alpha-hydroxybutyric acid and defective that α-the alpha-ketobutyric acid price is higher.
Of the present invention is the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol, and step is:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 2～4 times with pH 72～7.5 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 5～120 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 5～60 grams per liters, and adds disodium ethylene diamine tetraacetate to 5～40 mM/ls of final concentrations; At 20～50 ℃, under pH 4.0～10.0 conditions, with 50～180 rev/mins of vibrations 1～30 hour, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 5,000～10,000 rev/min centrifugal 5～25 minutes, perhaps use 200～400 order filter-cloth filterings, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
R-alpha-hydroxybutyric acid content detection employing Agilentl100 high pressure liquid chromatography system, chromatographic column is Aminex HPX-87H; Analysis condition is that 55 ℃ of column temperatures, flow velocity are 0.4 ml/min take 10 mM/ls of sulfuric acid as moving phase, and sample size 5 microlitres adopt differential refraction detector.
R-alpha-hydroxybutyric acid enantiomeric excess pH-value determination pH employing Agilentl100 high pressure liquid chromatography system, chromatographic column is (50 * 4.6 millimeters of chiral columns, MCIGEL CRS10W, the Mitsubishi chemistry), as moving phase, 25 ℃ of column temperatures, flow velocity are 0.5 ml/min with 2 mM/ls of copper sulfate solutions, sample size 5 microlitres, UV-detector wavelength are 254 nanometers.Testing sample is with perchloric acid (5%) acidifying of two volumes, 4 ℃ after standing 2 hours, 12000 rev/mins centrifugal 15 minutes, centrifugal supernatant is with the water membrane filtration of 0.22 micron, then stratographic analysis.Enantiomeric excess value=(R-alpha-hydroxybutyric acid content-S-alpha-hydroxybutyric acid content) ÷ (R-alpha-hydroxybutyric acid content+S-alpha-hydroxybutyric acid content) * 100%.
Above-mentioned is that substrate is produced in the method for R-alpha-hydroxybutyric acid with 1,2-butyleneglycol:
Step (2) is described 1, and 2-butyleneglycol concentration is preferably 10～50 grams per liters.
The described biological catalyst of step (2) be the concentration of intact cell be preferably 40～100 gram wet cells/liter.
The described disodium ethylene diamine tetraacetate concentration of step (2) is preferably 10～30 mM/ls.
The described temperature of step (2) is preferably 25～40 ℃.
The described pH of step (2) is preferably 5.0～8.0.
The described duration of oscillation of step (2) is preferably 4～25 hours.
It is the intact cell of bacillus of oxidizing glucose DSM 2003 that the present invention utilizes biological catalyst, and optionally oxidation 1, and 1 hydroxyl of 2-butyleneglycol realizes that successfully the stereospecificity of R-alpha-hydroxybutyric acid is synthetic.The inventive method has following characteristics:
(1) adopt the method for biocatalysis, reaction system is simple, and reaction conditions is gentle, and step is brief, and is easy and simple to handle.Biological catalyst can easily be removed, and is convenient to the subsequent products separation and purification.
(2) reaction time shorter, product R-alpha-hydroxybutyric acid can run up to higher concentration.
(3) substrate 1, and the 2-butyleneglycol is cheap, is easy to obtain.
(4) product enantiomeric excess rate is high, can reach more than 99%.
Description of drawings
Fig. 1 R-alpha-hydroxybutyric acid standard substance high pressure liquid chromatography detected result.
Fig. 2 S-alpha-hydroxybutyric acid standard substance high pressure liquid chromatography detected result.
Fig. 3 R-alpha-hydroxybutyric acid product high pressure liquid chromatography detected result.
Fig. 4 R-alpha-hydroxybutyric acid product mass spectrometric detection result.
Embodiment
Embodiment 1:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003 (buying from German microbial preservation center), ordinary method is cultivated, separate and collect thalline, wash thalline 3 times with pH 7.4 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 60 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 40 grams per liters, and adds disodium ethylene diamine tetraacetate to 20 mM/ls of final concentrations; At 37 ℃, under pH 6.0 conditions, with 180 rev/mins of vibrations 25 hours, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 10,000 rev/mins centrifugal 15 minutes, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
Detect through HPLC, by comparing R-2-hydroxybutyric acid standard substance high pressure liquid chromatography results (Fig. 1) and S-2-hydroxybutyric acid standard substance high pressure liquid chromatography results (Fig. 2) and R-2-hydroxybutyric acid product high pressure liquid chromatography result (Fig. 3), find that in step (3) gained supernatant liquor, the product retention time is consistent with R-2-hydroxybutyric acid standard substance, its molecular weight of mass spectrometric detection conform to the R-2-hydroxybutyric acid (Fig. 4).Confirm that thus biological catalyst is that the product that bacillus of oxidizing glucose DSM 2003 intact cells transform 1,2-butyleneglycols is the R-2-hydroxybutyric acid, and to measure its concentration be 18.2 grams per liters, enantiomeric excess value is 99.7%.
Embodiment 2:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 3 times with pH 7.4 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 100 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 50 grams per liters, and adds disodium ethylene diamine tetraacetate to 30 mM/ls of final concentrations; At 40 ℃, under pH 4.0 conditions, with 180 rev/mins of vibrations 15 hours, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 10,000 rev/mins centrifugal 15 minutes, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
After testing, in step (3), the concentration of contained R-2-hydroxybutyric acid is 11.2 grams per liters, and enantiomeric excess value is 95.3%.
Embodiment 3:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 3 times with pH 7.4 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 120 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 60 grams per liters, and adds disodium ethylene diamine tetraacetate to 40 mM/ls of final concentrations; At 40 ℃, under pH 5.0 conditions, with 180 rev/mins of vibrations 30 hours, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 10,000 rev/mins centrifugal 15 minutes, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
After testing, in step (3), the concentration of contained R-2-hydroxybutyric acid is 21.2 grams per liters, and enantiomeric excess value is 97.6%.
Embodiment 4:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 3 times with pH 7.4 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 5 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 5 grams per liters, and adds disodium ethylene diamine tetraacetate to 20 mM/ls of final concentrations; At 50 ℃, under pH 8.0 conditions, with 180 rev/mins of vibrations 1 hour, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 10,000 rev/mins centrifugal 15 minutes, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
After testing, in step (3), the concentration of contained R-2-hydroxybutyric acid is 0.2 grams per liter, and enantiomeric excess value is 96.6%.
Embodiment 5:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 3 times with pH 7.4 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 60 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 40 grams per liters, and adds disodium ethylene diamine tetraacetate to 10 mM/ls of final concentrations; At 20 ℃, under pH 10.0 conditions, with 180 rev/mins of vibrations 24 hours, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 10,000 rev/mins centrifugal 15 minutes, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
After testing, in step (3), the concentration of contained R-2-hydroxybutyric acid is 2.2 grams per liters, and enantiomeric excess value is 96.4%.
Embodiment 6:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 3 times with pH 7.4 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
Wherein, above-mentioned bacillus of oxidizing glucose uses following culture medium prescription to cultivate: D-glucitol 80 grams per liters; Yeast powder 24 grams per liters; Ammonium sulfate 5 grams per liters; Potassium primary phosphate 2 grams per liters; Sal epsom 5 grams per liters; Calcium carbonate 10 grams per liters.
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 60 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 60 grams per liters, and adds disodium ethylene diamine tetraacetate to 20 mM/ls of final concentrations; At 30 ℃, under pH 6.0 conditions, with 180 rev/mins of vibrations 24 hours, obtain conversion fluid.
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 10,000 rev/mins centrifugal 15 minutes, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
(4) detection of product R-alpha-hydroxybutyric acid
After testing, in step (3), the concentration of contained R-2-hydroxybutyric acid is 23.2 grams per liters, and enantiomeric excess value is 98.4%.
Claims (7)
1. method of producing the R-alpha-hydroxybutyric acid take the 2-butyleneglycol as substrate, step is:
(1) preparation biological catalyst
Choose bacillus of oxidizing glucose DSM 2003, ordinary method is cultivated, separate and collect thalline, wash thalline 2～4 times with pH 7.2～7.5 potassium phosphate buffers, thalline is resuspended in deionized water, make cell concentration reach 200 gram wet cells/liter, the intact cell suspension that obtains is biological catalyst, 4 ℃ store for future use;
(2) transform
Be intact cell and substrate 1 with the biological catalyst that makes in step (1), 2-butyleneglycol aqueous solution, the concentration that makes biological catalyst in mixture be 5～120 gram wet cells/liter, 1, the concentration of 2-butyleneglycol is 5～60 grams per liters, and adds disodium ethylene diamine tetraacetate to 5～40 mM/ls of final concentrations; At 20～50 ℃, under pH 4.0～10.0 conditions, with 50～180 rev/mins of vibrations 1～30 hour, obtain conversion fluid;
(3) produce and contain R-alpha-hydroxybutyric acid solution
With the conversion fluid that makes in step (2) with 5,000～10,000 rev/min centrifugal 5～25 minutes, perhaps use 200～400 order filter-cloth filterings, removing biological catalyst is intact cell, the gained clear liquid is and contains R-alpha-hydroxybutyric acid solution.
2. be the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol as claimed in claim 1, it is characterized in that, step (2) is described 1, and 2-butyleneglycol concentration is 10～50 grams per liters.
3. be the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol as claimed in claim 1, it is characterized in that, the described biological catalyst of step (2) be the concentration of intact cell be 40～100 gram wet cells/liter.
4. be the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol as claimed in claim 1, it is characterized in that, the described disodium ethylene diamine tetraacetate concentration of step (2) is 10～30 mM/ls.
5. be the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol as claimed in claim 1, it is characterized in that, the described temperature of step (2) is 25～40 ℃.
6. be the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol as claimed in claim 1, it is characterized in that, the described pH of step (2) is 5.0～8.0.
7. be the method that substrate is produced the R-alpha-hydroxybutyric acid with 1,2-butyleneglycol as claimed in claim 1, it is characterized in that, the described duration of oscillation of step (2) is 4～25 hours.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109097314A (en) * | 2018-07-24 | 2018-12-28 | 山东大学 | A method of the full cell of Gluconobacter oxvdans is prepared by carbon source of glycerol |
| CN114773180A (en) * | 2022-04-28 | 2022-07-22 | 浙江大学 | Synthesis method and catalyst for preparing 3-hydroxybutyric acid through selective oxidation of 1, 3-butanediol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101928734A (en) * | 2009-11-13 | 2010-12-29 | 山东大学 | Method for preparing alpha-ketobutyric acid |
| CN101974603A (en) * | 2010-09-30 | 2011-02-16 | 山东大学 | Method for producing D-alpha-hydroxybutyric acid |
-
2011
- 2011-11-10 CN CN201110355171.2A patent/CN103103222B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101928734A (en) * | 2009-11-13 | 2010-12-29 | 山东大学 | Method for preparing alpha-ketobutyric acid |
| CN101974603A (en) * | 2010-09-30 | 2011-02-16 | 山东大学 | Method for producing D-alpha-hydroxybutyric acid |
Non-Patent Citations (2)
| Title |
|---|
| 《食品与发酵工业》 20101231 魏国栋等 氧化葡萄糖酸杆菌立体选择催化2-甲基-1，3-丙二醇合成(R)-beta-羟基异丁酸 第12-16页 1-7 第36卷, 第8期 * |
| 魏国栋等: "氧化葡萄糖酸杆菌立体选择催化2-甲基-1，3-丙二醇合成(R)-β-羟基异丁酸", 《食品与发酵工业》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109097314A (en) * | 2018-07-24 | 2018-12-28 | 山东大学 | A method of the full cell of Gluconobacter oxvdans is prepared by carbon source of glycerol |
| CN114773180A (en) * | 2022-04-28 | 2022-07-22 | 浙江大学 | Synthesis method and catalyst for preparing 3-hydroxybutyric acid through selective oxidation of 1, 3-butanediol |
| CN114773180B (en) * | 2022-04-28 | 2023-11-17 | 浙江大学 | Synthetic method and catalyst for preparing 3-hydroxybutyric acid by selective oxidation of 1, 3-butanediol |
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