CN106977442A - 一种羟脯氨酸的提取工艺 - Google Patents
一种羟脯氨酸的提取工艺 Download PDFInfo
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- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 title claims abstract description 35
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229960002591 hydroxyproline Drugs 0.000 title claims abstract description 35
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 238000000605 extraction Methods 0.000 title claims description 13
- 239000000706 filtrate Substances 0.000 claims abstract description 13
- 239000003957 anion exchange resin Substances 0.000 claims abstract description 7
- 239000003729 cation exchange resin Substances 0.000 claims abstract description 7
- 239000013078 crystal Substances 0.000 claims abstract description 5
- 238000003828 vacuum filtration Methods 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000919 ceramic Substances 0.000 claims abstract description 4
- 239000012528 membrane Substances 0.000 claims abstract description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- 239000012610 weak anion exchange resin Substances 0.000 claims description 3
- 239000012608 weak cation exchange resin Substances 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 230000010355 oscillation Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 10
- 238000000855 fermentation Methods 0.000 abstract description 8
- 230000004151 fermentation Effects 0.000 abstract description 8
- 239000007788 liquid Substances 0.000 abstract description 6
- 239000000047 product Substances 0.000 abstract description 6
- 238000002390 rotary evaporation Methods 0.000 abstract description 6
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 abstract description 5
- 239000002699 waste material Substances 0.000 abstract description 5
- 238000004042 decolorization Methods 0.000 abstract description 4
- 238000000108 ultra-filtration Methods 0.000 abstract description 3
- 239000012452 mother liquor Substances 0.000 abstract description 2
- 241000894006 Bacteria Species 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000009776 industrial production Methods 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000010865 sewage Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Organic Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
本发明提供了一种羟脯氨酸的提取工艺，通过将羟脯氨酸发酵液过陶瓷膜除去菌体，然后将滤液pH调至6.5以下，过阴离子交换树脂，流出液的pH调至6.5以上，过阳离子交换树脂，将流出液减压蒸发至干燥后，用无水乙醇洗出，超声波振荡30min，最后再通过真空抽滤得到羟脯氨酸晶体；所述方法不需要经过超滤和活性炭脱色，可显著降低废污处理难度，同时旋转蒸发至干燥，减少了母液中羟脯氨酸的残留量，使得产品收率高、纯度高、质量稳定。
Description
技术领域
本发明涉及生物化工技术领域，尤其是一种羟脯氨酸的提取工艺。
背景技术
羟脯氨酸是胶原蛋白的主要组成成分，它广泛应用于医药、化工、动物饲料和美容等方面。生产羟脯氨酸的方法主要有化学合成法、生物提取法和微生物发酵法。化学合成法成本高，不适合用于工业化生产。目前国内生产羟脯氨酸主要方法是生物提取法，然而利用生物提取法从明胶、胶原、猪皮中直接提取羟脯氨酸有诸多弊端，不仅生产和纯化的步骤多、产率低、原料利用率低，而且在生产过程中需加入大量的化工试剂，环境污染大，废水废渣难处理。利用微生物发酵法生产羟脯氨酸，不仅可降低原料成本，提高生产效率，而且用可再生资源代替化工类等不可再生资源，降低了对环境的污染。因此，利用微生物发酵法生产羟脯氨酸具有重要意义。
目前，发酵液中羟脯氨酸提取工艺为发酵液通过微滤和超滤得到滤液后，过离子交换树脂，洗脱得到含羟脯氨酸的滤液后，加入0.5％活性炭脱色，然后经过真空抽滤得滤液，将滤液旋转蒸发浓缩体积至原液的1/7-1/8，真空抽滤得到羟脯氨酸晶体。由于该方法需要使用活性炭进行脱色处理，在工业化生产时，大量的活性炭会造成废污处理难度，污染环境；在旋转蒸发时，剩余的少量液体会使部分羟脯氨酸溶解在其中，造成产品收率较低。
发明内容
本发明所要解决的技术问题在于提供一种羟脯氨酸的提取工艺。
为解决上述技术问题，本发明的技术方案是：
一种羟脯氨酸的提取工艺，具体步骤如下：
(1)将羟脯氨酸发酵液(常规发酵液)过陶瓷膜除去菌体得滤液；
(2)用盐酸溶液将滤液pH调至5.5-6.0，过阴离子交换树脂收集第一次流出液；
(3)用氨水将第一次流出液pH调至7.0-7.5，过阳离子交换树脂，收集第二次流出液；
(4)将第二次流出液旋转蒸发至干燥，用无水乙醇洗出，超声波振荡30min；
(5)真空抽滤得到羟脯氨酸晶体。
优选的，上述羟脯氨酸的提取工艺，所述阴离子交换树脂为通过盐酸或硫酸转型为氯型弱阴离子交换树脂或硫酸根型阴离子交换树脂。
优选的，上述羟脯氨酸的提取工艺，所述阳离子交换树脂为经过NaCl溶液或氨水转型为钠型弱阳离子交换树脂或铵根离子型阳离子交换树脂。
本发明结构有如下有益效果：
上述羟脯氨酸的提取工艺，与传统工艺相比，不需要经过超滤和活性炭脱色，可显著降低废污处理难度，减轻了废污处理负担，同时旋转蒸发至干燥，减少了母液中羟脯氨酸的残留量，使得产品收率高、纯度高、质量稳定可靠；整个工艺过程操作简单，成本较低，十分适用于工业化生产。
具体实施方式
为进一步说明本发明，现通过具体实施实例对本发明进行详细阐述。
一种羟脯氨酸提取新工艺，包括以下步骤：
取羟脯氨酸发酵液(含羟脯氨酸为37.7g/L)过陶瓷膜除去菌体得滤液，将滤液pH调至5.5-6.0，过弱阴离子交换树脂SQD817(过30倍床体积的滤液)，除去色素及蛋白，得到羟脯氨酸流出液，将流出液pH调至7.0-7.5，过弱阳离子交换树脂D152(过100倍床体积的滤液)，对色素和蛋白进行二次去除，流出液采用旋转蒸发仪在75℃左右蒸发浓缩至干燥，然后用无水乙醇洗出，超声波振荡30min，洗去残留色素，最后通过真空抽滤得到羟脯氨酸晶体。计算得到，从旋转蒸发至得到羟脯氨酸产品的一步收率达92％，与原工艺(从旋转蒸发至得到羟脯氨酸产品的一步收率为70％)相比，提高了31.4％。产品纯度达99.6％。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (3)
1.一种羟脯氨酸的提取工艺，其特征在于：具体步骤如下：
(1)将羟脯氨酸发酵液过陶瓷膜除去菌体得滤液；
(2)将滤液pH调至5.5-6.0，过阴离子交换树脂，收集第一次流出液；
(3)第一次流出液pH调至7.0-7.5，过阳离子交换树脂，收集第二次流出液；
(4)将第二次流出液旋转蒸发至干燥，用无水乙醇洗出，超声波振荡30min；
(5)真空抽滤得到羟脯氨酸晶体。
2.根据权利要求1所述的羟脯氨酸的提取工艺，其特征在于：所述阴离子交换树脂为通过盐酸或硫酸转型为氯型弱阴离子交换树脂或硫酸根型阴离子交换树脂。
3.根据权利要求1所述的羟脯氨酸的提取工艺，其特征在于：所述阳离子交换树脂为经过NaCl溶液或氨水转型为钠型弱阳离子交换树脂或铵根离子型阳离子交换树脂。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107513030A (zh) * | 2017-10-19 | 2017-12-26 | 福建师范大学 | 一种从l‑羟脯氨酸发酵液中分离纯化l‑羟脯氨酸的方法 |
| WO2020113289A1 (en) * | 2018-12-07 | 2020-06-11 | Atp Institute Pty Ltd | Formulations comprising non-animal derived hydroxyproline and their use |
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|---|---|---|---|---|
| JPH07289274A (ja) * | 1994-04-26 | 1995-11-07 | Sankyo Co Ltd | トランス−４−ヒドロキシ−ｌ−プロリンの製造法 |
| EP0547898B1 (en) * | 1991-12-17 | 1999-02-17 | Sankyo Company Limited | Microbial process for the production of trans-4-hydroxy-L-proline |
| CN105420303A (zh) * | 2015-12-09 | 2016-03-23 | 浙江绿创生物科技有限公司 | 一种生产反式-4-羟基-l-脯氨酸的发酵工艺 |
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| CN107827803A (zh) * | 2017-11-28 | 2018-03-23 | 绍兴厚普生物科技有限责任公司 | 一种从发酵液中提取l‑羟脯氨酸的方法 |
-
2017
- 2017-04-28 CN CN201710290318.1A patent/CN106977442A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0547898B1 (en) * | 1991-12-17 | 1999-02-17 | Sankyo Company Limited | Microbial process for the production of trans-4-hydroxy-L-proline |
| JPH07289274A (ja) * | 1994-04-26 | 1995-11-07 | Sankyo Co Ltd | トランス−４−ヒドロキシ−ｌ−プロリンの製造法 |
| CN105420303A (zh) * | 2015-12-09 | 2016-03-23 | 浙江绿创生物科技有限公司 | 一种生产反式-4-羟基-l-脯氨酸的发酵工艺 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107513030A (zh) * | 2017-10-19 | 2017-12-26 | 福建师范大学 | 一种从l‑羟脯氨酸发酵液中分离纯化l‑羟脯氨酸的方法 |
| WO2020113289A1 (en) * | 2018-12-07 | 2020-06-11 | Atp Institute Pty Ltd | Formulations comprising non-animal derived hydroxyproline and their use |
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