甜菊苷的酶促糖基化和水解反应研究
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摘要
甜菊糖是从甜叶菊中提取的系列高倍低热值甜味剂，同时兼具多种生物活性，是最理想的蔗糖替代品。甜菊苷(St)是甜叶菊提取物中含量最高的组分，但它的后苦涩味限制了它在食品、饮料等领域中的应用。本文以甜菊苷的脱苦及其高附加值衍生物开发为目的，分别利用多种糖基转移酶和水解酶催化转化甜菊苷，发掘糖酶的新催化性能，通过研究其差向催化行为和过程动力学，首先获得脱除了后苦涩味的甜菊苷葡萄糖基化合物，其次分别通过选择性水解甜菊苷中的三个葡萄糖基，得到多种自然界存在的稀少甜菊苷衍生物。同时初步考查了连续微波辐射在甜菊苷的转苷和水解反应中的应用。
在糖基化反应中，环糊精葡萄糖基转移酶(CGTase)在实验所用糖基转移酶中的转苷活性最高。用来源于Paenibacillus macerans JFB05-01的α-CGTase催化St的转苷反应，得到6种以上转苷产物。利用聚丙烯酰胺凝胶柱和硅胶层析柱分离出转苷产物中味质最佳的转苷产物，即接枝一个葡萄基产物产物(St-Glu1)。优化了转苷反应条件：水为反应介质，底物比为m (淀粉水解液)∶m (St)=1.5∶1，加酶量15U/g St，60oC下反应3h可达平衡，St最高底物浓度高达150mg/mL，St的转化率为59.2%，St-Glu1的产率为32.4%。转苷产物经淀粉糖化酶水解0.75h后，转苷产物中St-Glu1含量提高1.6倍，St上连接3个以上葡萄糖基的转苷产物仅占1.1%。转苷产物甜度略微降低，但后苦涩味明显改善，并且在水中的溶解度提高60倍以上。但产物的热稳定性不如甜菊苷和莱鲍迪苷A，120oC下开始分解。
在糖基水解酶选择性催化甜菊苷的水解反应中，来源于Aspergillus sp.的β-半乳糖苷酶能够高选择性催化水解St的C13位槐糖基的β-1,2葡萄糖苷键得到悬钩子苷。该酶还表现出较弱的转苷活性，但即使在高浓度糖基供体的存在下，反应体系仍选择水解反应为主反应。该β-半乳糖苷酶具有较强的底物特异性，对莱鲍迪苷A、莱鲍迪苷C等St类似物的催化活性较弱，但能催化水解甜菊双糖苷制备甜菊单糖苷。水解最优条件为：60oC下，以水为介质，St的浓度为80mg/mL，加酶量为0.8KU/gSt时，反应72h，St的转化率为98.3%，Ru的产率为91.4%。Ca~(2+)、Co~(2+)、Mn~(2+)和Mg~(2+)能够提高酶的催化活性。水解反应的K_m和V_(max)分别为0.344mol/L和4315.1mol/L·min。制得的悬钩子苷性能优于市售从甜茶中提取的产品。与St相比，悬钩子苷甜度略微降低但溶解度大大提高；并且悬钩子苷对St具有增溶作用，3mg/mL的悬钩子苷溶液中，St的溶解度提高6.25倍。
此外，来源于Kluyveromyces lactis的β-半乳糖苷酶可以选择性水解St中C19位糖酯键，得到甜菊双糖苷。37.5oC，底物浓度为25mg/mL，加酶量为16000NLU/g St，12h时St的转化率为99.5%。而来源于Sulfolobus sp.的β-半乳糖苷酶能够水解St所有三个糖苷键，得到甜菊醇。75oC，底物浓度为20mg/mL，加酶量为625U/g St，pH4.6下，反应6h后St最终转化率为99.0%，并有望实现反应耦合分离。
初步考查了连续微波辐射对糖苷酶催化St转苷或水解反应的影响。仅来源于Paenibacillusmacerans JFB05-01的α-CGTase催化St转苷反应在微波辐射模式下表现出较高的催化活性。相同条件下，微波辐射比常规加热时催化效率提高了21.7倍，反应1min St的转化率可达32.6%。优化了连续微波辐射模式下反应条件：20W，1min，55oC，m (淀粉水解液)∶m (St)=1∶1，以水为溶剂，St初始底物浓度最高可达200mg/mL，加酶量为10U/g St时，转化率为52.5%，St-Glu1的含量为21.5%，当加酶量为1000U/g，反应1min St的转化率高达71.6%，St-Glu1的含量为23.7%。与常规加热下的催化反应相比，连续微波辐射下达到相同转化率的反应时间大大缩短，但连续微波辐射下更能促进高接枝产物的生成。
除了甜度和溶解度外，实验比较了甜菊醇、异甜菊醇、悬钩子苷和甜菊双糖苷以及甜菊苷、莱鲍迪苷A和莱鲍迪苷C的羟基自由基清除能力，发现甜菊醇衍生物的糖基数量与羟基自由基清除能力相关。
Steviol glycosides are widely used as low-calorie intensive sweeteners obtained from Steviarebaudiana. They are the most ideal sucrose substitutes in nature and possess many bioactivities. Stevioside(St) is one of the main components in the extract; however, its bitterness aftertaste affects its application infood and beverage. The aim of this dissertation is to elimite the bitterness aftertaste of St and develop highvalue-added St derivatives. In this experiment, several glycosyltransferases and glycosyl hydrolases havebeen utilized to catalyze the conversion of St, and novel catalysis activities were found. Based on studies onthe catalysis behavior and process kinetics, transglycosylation products were obtained with improvedsweetness and no more bitterness aftertaste. Subsquntly, some rare St derivatives existed in nature wereprepared through regioselective hydrolysis of the three glycosidic linkages in St, respectivly. In addition,microwave irradiated transglycosylation and hydrolysis were investigated.
The cyclodextrin glucosyltransferase (CGTase) showed the best transglycosylation activity among ofall assayed enzymes. In the transglycosylation catalyzed by α-CGTase from Paenibacillus maceransJFB05-01, more than6transglycosylation products were produced, and the mono-glucosyl stevioside(St-Glu1) presented the best taste. The optimized transglycosylation conditions were: the mass ratio ofstarch hydrolysate to St was1.5:1,150mg/mL St in DI water with15U/g St of the enzyme, the Stconversion and St-Glu1yield reached59.2%and32.4%in3h at60oC, respectively. The hydrolysis oftransglycosylated products with glucoamylase increased St-Glu1content1.6folds, and left the tri-glucosylstevioside and higher grafted St in a content less than1.1%.
Enzymatic hydrolysis of St was studied using some glycosyl hydrolases. A natural sweetenerrubusosidewas prepared from the specific hydrolysis of β-1,2glucosidic linkage of St with β-galactosidasefrom Aspergillus sp. This β-galactosidase showed lower transglycosylation activity accompanying with thehydrolysis of St, even in the presence of additional donors. The β-galactosidase also possesses substratespecificity in hydrolysis. Analogues of St, such as rebaudioside A, rebaudioside C, etc. can’t be hydrolyzedusing the β-galactosidase. However, steviolmonoside was produced from hydrolysis of steviolbioside withthis enzyme. Optimal hydrolysis conditions were:60oC in DI water with a substrate concentration of80mg/mL, St conversion and rubusoside yield reached98.3%and91.4%in6h, respectively. The activity ofenzyme can be improved by Ca~(2+), Co~(2+), Mn~(2+)and Mg~(2+). The synthetic rubusoside tastes better than thecommercial rubusoside extracted from Rubus Suavissimus. rubusoside has a higher solubility than St, andcan improve the solubility of St. In a solution of3mg/mL rubusoside, the St solubility increased6.25folds.
Subsequently, the ester linkage at C19of St was hydrolyzed selectively using the β-galactosidase fromKluyveromyces lactis with steviolbioside as the only hydrolysis product. St conversion reached99.5%at12h under37.5oC,25mg St/mL and16000NLU/g St. Besides of aforementioned transglycoslyationactivity, the β-galactosidase from Sulfolobus sp. can cleavage all three glycosides of St to release steviolThe conversion of St reached99.0%using20mg/mL of St and625U/g St of enzyme at pH4.6,75oC, in6h. The in-situ purification in the reaction could be realized because of the big difference between thesolubilities of products and materials.
Microwave irradiation assisted transglycosylation and hydrolysis of St were investigated. Onlyα-CGTase from Paenibacillus macerans JFB05-01showed higher activity under irradiation comparing tothat with conventional heating, the catalytic efficiency under irradiation increased21.7folds under thesame conditions. The optimized transglycosylation conditions were:20W,55oC,1000U/g St of enzyme,the mass ratio of starch hydrolysate to St was1:1,200mg/mL of St, St conversion reached71.6%with23.7%of St-Glu1yield in1min. Microwave irradiation was more efficient than conventional heating for shortentime, but which does not favor to yield St-Glu1.
Besides of sweetness and solubility, antiradical activity of steviol glycosides, steviol, isosteviol,rubusoside, steviolbioside, stevioside, rebaudioside A and rebaudioside C was compared. The amount ofglucose of steviol glycosides and antiradical activity was related.
在糖基化反应中，环糊精葡萄糖基转移酶(CGTase)在实验所用糖基转移酶中的转苷活性最高。用来源于Paenibacillus macerans JFB05-01的α-CGTase催化St的转苷反应，得到6种以上转苷产物。利用聚丙烯酰胺凝胶柱和硅胶层析柱分离出转苷产物中味质最佳的转苷产物，即接枝一个葡萄基产物产物(St-Glu1)。优化了转苷反应条件：水为反应介质，底物比为m (淀粉水解液)∶m (St)=1.5∶1，加酶量15U/g St，60oC下反应3h可达平衡，St最高底物浓度高达150mg/mL，St的转化率为59.2%，St-Glu1的产率为32.4%。转苷产物经淀粉糖化酶水解0.75h后，转苷产物中St-Glu1含量提高1.6倍，St上连接3个以上葡萄糖基的转苷产物仅占1.1%。转苷产物甜度略微降低，但后苦涩味明显改善，并且在水中的溶解度提高60倍以上。但产物的热稳定性不如甜菊苷和莱鲍迪苷A，120oC下开始分解。
在糖基水解酶选择性催化甜菊苷的水解反应中，来源于Aspergillus sp.的β-半乳糖苷酶能够高选择性催化水解St的C13位槐糖基的β-1,2葡萄糖苷键得到悬钩子苷。该酶还表现出较弱的转苷活性，但即使在高浓度糖基供体的存在下，反应体系仍选择水解反应为主反应。该β-半乳糖苷酶具有较强的底物特异性，对莱鲍迪苷A、莱鲍迪苷C等St类似物的催化活性较弱，但能催化水解甜菊双糖苷制备甜菊单糖苷。水解最优条件为：60oC下，以水为介质，St的浓度为80mg/mL，加酶量为0.8KU/gSt时，反应72h，St的转化率为98.3%，Ru的产率为91.4%。Ca~(2+)、Co~(2+)、Mn~(2+)和Mg~(2+)能够提高酶的催化活性。水解反应的K_m和V_(max)分别为0.344mol/L和4315.1mol/L·min。制得的悬钩子苷性能优于市售从甜茶中提取的产品。与St相比，悬钩子苷甜度略微降低但溶解度大大提高；并且悬钩子苷对St具有增溶作用，3mg/mL的悬钩子苷溶液中，St的溶解度提高6.25倍。
此外，来源于Kluyveromyces lactis的β-半乳糖苷酶可以选择性水解St中C19位糖酯键，得到甜菊双糖苷。37.5oC，底物浓度为25mg/mL，加酶量为16000NLU/g St，12h时St的转化率为99.5%。而来源于Sulfolobus sp.的β-半乳糖苷酶能够水解St所有三个糖苷键，得到甜菊醇。75oC，底物浓度为20mg/mL，加酶量为625U/g St，pH4.6下，反应6h后St最终转化率为99.0%，并有望实现反应耦合分离。
初步考查了连续微波辐射对糖苷酶催化St转苷或水解反应的影响。仅来源于Paenibacillusmacerans JFB05-01的α-CGTase催化St转苷反应在微波辐射模式下表现出较高的催化活性。相同条件下，微波辐射比常规加热时催化效率提高了21.7倍，反应1min St的转化率可达32.6%。优化了连续微波辐射模式下反应条件：20W，1min，55oC，m (淀粉水解液)∶m (St)=1∶1，以水为溶剂，St初始底物浓度最高可达200mg/mL，加酶量为10U/g St时，转化率为52.5%，St-Glu1的含量为21.5%，当加酶量为1000U/g，反应1min St的转化率高达71.6%，St-Glu1的含量为23.7%。与常规加热下的催化反应相比，连续微波辐射下达到相同转化率的反应时间大大缩短，但连续微波辐射下更能促进高接枝产物的生成。
除了甜度和溶解度外，实验比较了甜菊醇、异甜菊醇、悬钩子苷和甜菊双糖苷以及甜菊苷、莱鲍迪苷A和莱鲍迪苷C的羟基自由基清除能力，发现甜菊醇衍生物的糖基数量与羟基自由基清除能力相关。
Steviol glycosides are widely used as low-calorie intensive sweeteners obtained from Steviarebaudiana. They are the most ideal sucrose substitutes in nature and possess many bioactivities. Stevioside(St) is one of the main components in the extract; however, its bitterness aftertaste affects its application infood and beverage. The aim of this dissertation is to elimite the bitterness aftertaste of St and develop highvalue-added St derivatives. In this experiment, several glycosyltransferases and glycosyl hydrolases havebeen utilized to catalyze the conversion of St, and novel catalysis activities were found. Based on studies onthe catalysis behavior and process kinetics, transglycosylation products were obtained with improvedsweetness and no more bitterness aftertaste. Subsquntly, some rare St derivatives existed in nature wereprepared through regioselective hydrolysis of the three glycosidic linkages in St, respectivly. In addition,microwave irradiated transglycosylation and hydrolysis were investigated.
The cyclodextrin glucosyltransferase (CGTase) showed the best transglycosylation activity among ofall assayed enzymes. In the transglycosylation catalyzed by α-CGTase from Paenibacillus maceransJFB05-01, more than6transglycosylation products were produced, and the mono-glucosyl stevioside(St-Glu1) presented the best taste. The optimized transglycosylation conditions were: the mass ratio ofstarch hydrolysate to St was1.5:1,150mg/mL St in DI water with15U/g St of the enzyme, the Stconversion and St-Glu1yield reached59.2%and32.4%in3h at60oC, respectively. The hydrolysis oftransglycosylated products with glucoamylase increased St-Glu1content1.6folds, and left the tri-glucosylstevioside and higher grafted St in a content less than1.1%.
Enzymatic hydrolysis of St was studied using some glycosyl hydrolases. A natural sweetenerrubusosidewas prepared from the specific hydrolysis of β-1,2glucosidic linkage of St with β-galactosidasefrom Aspergillus sp. This β-galactosidase showed lower transglycosylation activity accompanying with thehydrolysis of St, even in the presence of additional donors. The β-galactosidase also possesses substratespecificity in hydrolysis. Analogues of St, such as rebaudioside A, rebaudioside C, etc. can’t be hydrolyzedusing the β-galactosidase. However, steviolmonoside was produced from hydrolysis of steviolbioside withthis enzyme. Optimal hydrolysis conditions were:60oC in DI water with a substrate concentration of80mg/mL, St conversion and rubusoside yield reached98.3%and91.4%in6h, respectively. The activity ofenzyme can be improved by Ca~(2+), Co~(2+), Mn~(2+)and Mg~(2+). The synthetic rubusoside tastes better than thecommercial rubusoside extracted from Rubus Suavissimus. rubusoside has a higher solubility than St, andcan improve the solubility of St. In a solution of3mg/mL rubusoside, the St solubility increased6.25folds.
Subsequently, the ester linkage at C19of St was hydrolyzed selectively using the β-galactosidase fromKluyveromyces lactis with steviolbioside as the only hydrolysis product. St conversion reached99.5%at12h under37.5oC,25mg St/mL and16000NLU/g St. Besides of aforementioned transglycoslyationactivity, the β-galactosidase from Sulfolobus sp. can cleavage all three glycosides of St to release steviolThe conversion of St reached99.0%using20mg/mL of St and625U/g St of enzyme at pH4.6,75oC, in6h. The in-situ purification in the reaction could be realized because of the big difference between thesolubilities of products and materials.
Microwave irradiation assisted transglycosylation and hydrolysis of St were investigated. Onlyα-CGTase from Paenibacillus macerans JFB05-01showed higher activity under irradiation comparing tothat with conventional heating, the catalytic efficiency under irradiation increased21.7folds under thesame conditions. The optimized transglycosylation conditions were:20W,55oC,1000U/g St of enzyme,the mass ratio of starch hydrolysate to St was1:1,200mg/mL of St, St conversion reached71.6%with23.7%of St-Glu1yield in1min. Microwave irradiation was more efficient than conventional heating for shortentime, but which does not favor to yield St-Glu1.
Besides of sweetness and solubility, antiradical activity of steviol glycosides, steviol, isosteviol,rubusoside, steviolbioside, stevioside, rebaudioside A and rebaudioside C was compared. The amount ofglucose of steviol glycosides and antiradical activity was related.
引文
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