CN109913508A - 一种利用蓝藻合成根皮素的方法 - Google Patents
一种利用蓝藻合成根皮素的方法 Download PDFInfo
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Abstract
本本发明提供一种以“光合细菌”—蓝藻为底盘生物来合成根皮素的技术方法，主要步骤是在蓝藻细胞里外源表达4香豆酸‑辅酶A连接酶（4 coumarate Coenzyme A Ligase，4CL）和查尔酮合成酶（Chalcone synthase，CHS）这两个根皮素合成关键酶，以对羟基苯丙酸（或称根皮酸）为底物来催化生成根皮素，4CL催化一分子对羟基苯丙酸生成对羟基苯丙酰辅酶A，然后CHS催化3个分子的丙二酰辅酶A（malonyl coA）与一分子对羟基苯丙酰辅酶A合成一分子根皮素。本方法通过一种可以进行光合作用的微生物来生产根皮素，从而创造了一种原料便宜、设备简单、环境污染低、产量高的根皮素生物合成途径，符合绿色化生产的方向。
Description
技术领域
本发明属于根皮素的合成技术领域，尤其涉及到一种利用蓝藻来生产根皮素的方法。
背景技术
蓝藻(Cyanobacteria)是一类通过光合作用获取能量的细菌，又名蓝绿藻、蓝绿菌或蓝细菌，其形态结构简单，无固定细胞核，体内含有的藻蓝蛋白和变藻蓝蛋白加上叶绿体蛋白使之呈现出蓝绿色。蓝藻是地球上最早出现的藻类，是最简单、最原始的单细胞生物，在漫长的进化过程中，蓝藻把地球变成氧化型地球，并被内吞成植物的叶绿体，可以认为蓝藻是最简单的光合作用单位。
由于蓝藻独特的能进行光合作用的生理特性，许多科学家将蓝藻看作一种“生物光反应器”，通过它将空气中的二氧化碳和水变成人类需要的化工产品和一些高价值的天然产物。对蓝藻进行基因改造来生物合成这些产品具有许多优势：（1）目前许多常见蓝藻的基因组，如聚球藻、集胞藻、鱼腥藻等，都已经被测序完毕，同时由于蓝藻的基因组小、结构简单，科学家已经发明了一套针对蓝藻细胞的成熟、易操作的基因编辑体系；（2）相对于高等动植物，蓝藻具有微生物生长快速的特点，适于进行产品的大规模生产操作；（3）蓝藻的适应能力很强，能在很多恶劣环境中生存，同时蓝藻需要的生存条件非常简单，甚至只需阳光和水分就能存活，因此在大规模培养时不仅能大幅度节省原料成本，而且不需要占用耕地资源，避免了和生产食物粮食等竞争土地资源的冲突。（4）蓝藻通过光合作用吸收空气中的二氧化碳并产生氧气排放到空中，因此大规模培养蓝藻能有效地缓解人类不断使用化石原料等造成的“温室效应”，起到一定的环保作用。所以使用蓝藻作为合成生物学中的底盘生物，具有广大的前景和巨大的价值。
根皮素英文名称：Phloretin；分子式：C15H14O5；化学名称：3-(4-羟基苯基)-1-(2、4、6-三羟基苯基)-1-丙酮；CAS：60-82-2；分子量：274.28；物理性质：易溶于甲醇、乙醇和丙酮，微溶于氯仿、难溶于水、石油醚和苯。
根皮素是国外新近研究开发出来的一种新型天然皮肤美白剂，主要分布于苹果、梨等多汁水果的果皮及根皮。根皮素能抑制皮脂腺的过度分泌，用于治疗分泌旺盛型粉刺；能抑制黑色素细胞活性，对各种皮肤色斑有作用。与同类天然成分熊果苷和曲酸相比，同等浓度的根皮素对酪氨酸酶的抑制作用要好于它们，并且当其与熊果苷和/或曲酸进行复配时，能大大提高产品对酪氨酸酶的抑制率，使抑制率达到100%。据最新研究发现其还有抗炎、免疫抑制，心血管保护等作用。全球每年用量不少于20吨，需求每年以20%速率增加，具有较大市场需求。
目前，市场上根皮素的生产主要是通过化工合成，有的以根皮苷粗品为原料，经过简单纯化根皮苷，再在强路易斯酸和金属催化拖糖元和结晶重结晶得到根皮素。还有的以柚皮苷为原料，兰尼镍为催化剂，在氢氧化钠溶液中，催化氢化10小时合成柚皮苷二氢查耳酮，然后在85℃-95℃下的盐酸溶液中，柚皮苷二氢查耳酮水解2小时得到根皮素。这些化工法合成根皮素存在效率低、化学废液的排放、严重污染环境等问题。现在也有开发一些利用大肠杆菌或酿酒酵母等发酵来生物合成根皮素的方法，虽然这些生物合成法解决了产量低和部分环境污染等问题，但由于生产过程中的原料、设备及水电等成本太高，无法实现大规模生产。
发明内容
本发明的目的在于解决现有技术的不足，提供一种利用蓝藻合成根皮素的生物合成方法，具有产量高、无污染、生产周期短、成本低且环保的优点。
一种利用蓝藻合成根皮素的方法，将4香豆酸-辅酶A连接酶基因（4CL）以及查尔酮合成酶基因（CHS），导入蓝藻细胞得到重组蓝藻细胞，利用重组蓝藻细胞进行光合作用得到根皮素。
优选地，所述蓝藻为聚球藻Synechococcus elongatus PCC7942。
该合成方法具体包括以下步骤：
构建整合载体NSI：选取所述Synechococcus elongatus PCC7942基因组上的基因序列段，且该段基因序列的改变不会影响Synechococcus elongatus PCC7942整个基因组的功能，以此来构建并获得整合载体NSI;
重组载体：根据Synechococcus elongatus PCC7942细胞密码子偏好性优化基因4CL和CHS的密码子，然后将这两个基因***到载体NSI上，得到带有氯霉素抗性基因的重组载体NSI-CHS-4CL；
同源重组：将重组载体NSI-CHS-4CL转化入Synechococcus elongatus PCC7942细胞内，通过同源重组作用，将CHS和4CL两个基因整合到Synechococcus elongatus PCC7942基因组上的NSI基因位点，并以诱导型启动子Trc来控制基因的表达。
筛选确认：以氯霉素来筛选转化NSI-CHS-4CL载体后的Synechococcus elongatus PCC7942单克隆细胞，然后提取该细胞基因组，通过PCR分子鉴定试验确定最终携带有4CL基因和CHS基因的Synechococcus elongatus PCC7942。
优选地，所述4CL根据向日葵中基因的氨基酸序列进行合成。
优选地，所述CHS根据灯盏花中基因的氨基酸序列进行合成。
本发明生产根皮素与现有技术的不同之处在于：
1）以蓝藻为底盘生物进行改造合成根皮素，生产原料仅需阳光和水分等，生产设备和生产环境构建简单，不需要大量用电，因此相较于其它生产方法，生产成本大幅度降低；
2）以改造微生物为技术基础，在微生物体内进行生物酶的催化合成，避免大规模的提取、分离、纯化过程，从生产成本和对环境友好方面容易控制；
3）本工艺在生产设备的规模和数量上比其他方法要要少，操作简单，易于产业转化；
4）本工艺仅在生产的最后步骤有分离纯化工序，产品纯化工艺简单，产品质量比一般方法纯度更好、含量更高；
5）合成过程没有废液排放，环境友好，无污染，可持续生产，本发明工艺从经济、环境和职业健康角度均为优良的工业化生产指路线。
附图说明
图1为本发明中外源基因整合示意图；
图2为本发明中NSI质粒图谱；
图3为本发明中重组载体NSI-CHS-4CL质粒图谱
图4为本发明中根皮素生物合成路线图；
图5为野生型Syn7942的液相结果图
图6为本发明中实施例的液相结果图；
图7为本发明中实施例的质谱图。
具体实施方式
为了使得本公开实施例的目的、技术方案和优点更加清楚，下面将结合本公开实施例的附图，对本公开实施例的技术方案进行清楚、完整地描述。显然，所描述的实施例是本公开的一部分实施例，而不是全部的实施例。基于所描述的本公开的实施例，本领域普通技术人员在无需创造性劳动的前提下所获得的所有其他实施例，都属于本公开保护的范围。
本发明公开了一种利用蓝藻合成根皮素的方法，包括在蓝藻细胞里外源表达4香豆酸-辅酶A连接酶（4 coumarate Coenzyme A Ligase， 4CL）和查尔酮合成酶（Chalconesynthase， CHS）这两个根皮素合成关键酶，以对羟基苯丙酸（又称根皮酸）为底物来催化生成根皮素，4CL催化一分子对羟基苯丙酸生成对羟基苯丙酰辅酶A，然后CHS催化3个分子的丙二酰辅酶A（malonyl coA）与一分子对羟基苯丙酰辅酶A合成一分子根皮素，主要包括构建整合载体NSI、重组载体、同源重组、筛选确认、催化合成以及检测六个步骤。
利用该合成方式，以蓝藻为底盘生物进行改造合成根皮素，生产原料仅需阳光和水分等，符合当今绿色生产的方向，且利用该生物手段，与化学提纯方式相比，本发明的生产设备和生产环境构建简单，不需要大量用电，生产成本大幅度降低的同时，有效保护了环境，实现了绿色化生产。
下面对本发明的几个实施例进行详细说明，但是本发明并不局限于这些具体实施例。
实施例一
本实施例提供载体质粒构建过程：根据本发明中提供的Synechococcus elongatus PCC7942（简称Syn7942）的NSI基因序列，按照附图2中的质粒图谱构建整合载体NSI，然后根据本发明中提供的4CL和CHS氨基酸序列，按照Syn7942细胞密码子偏好性设计相应基因的核酸序列，将基因4CL和CHS送市面上具有基因合成能力的公司合成，设计20bp左右大小的同源臂，按照附图3中的质粒图谱，利用一步克隆试剂盒，将这两个基因构建于整合载体NSI上。
NSI作为本发明提供的聚球藻Synechococcus elongatus PCC7942基因组上的一段基因序列， NSI的作用是，这段基因序列的改变不会影响聚球藻Synechococcus elongatus PCC7942整个基因组的功能，所以我们可以将外源基因（不是聚球藻Synechococcus elongatus PCC7942细胞内的基因）***到这个NSI这个基因序列上，这样既把外源基因整合到了Synechococcus elongatus PCC7942基因组上，同时又不会影响原有基因组的功能。
外源基因整合原理主要是通过基因同源重组，如图1所示，本发明在NSI基因序列上，分别在5’端和3’端各选1000bp左右的片段，将这两个片段分别连接在需要***的外源基因两端（如图1，图中上半部分是含有外源基因片段，上半部分是Synechococcus elongatus PCC7942的NSI基因序列），这样通过这个两个片段与NSI基因序列上的同源序列，就将外源基因重组到NSI上，CHS和4CL是需要表达的外源基因，其中，trc、lacl和Trrnb分别是启动子、操纵子和转入终止子元件共同用来控制基因表达，CM是氯霉素抗性基因，用来筛选含有外源基因的蓝藻。
实施例二
本实施例提供重组转化过程：
1)取2mL生长密度OD730为0.8~1.2的野生型Syn7942于离心管中，然后10000rpm，离心2min，去掉上清液；
2)用1mL 10mM氯化钠溶液混匀上一步中的沉淀物，然后10000rpm，离心2min，去掉上清液；
3)用1mL已灭菌的无抗BG11液体培养基混匀上一步中的沉淀物，然后10000rpm，离心2min，去掉上清液；
4)用100uL已灭菌的无抗BG11液体培养基混匀上一步中的沉淀物，然后向其中加入200ng的质粒DNA。用锡箔纸彻底密封该离心管（避光处理），然后在摇床中，100rpm，30℃培养10小时；
5)将上一步离心管中的蓝藻全部涂到含有25ug/mL氯霉素的BG11固体培养基上，将平板放入30℃光照培养箱中，待1到2个星期长出蓝藻单克隆后进行后续验证。
需要注意的是，除离心外，以上其余操作必须在超净台中完成，保证无菌环境。
实施例三
本实施例提供转基因蓝藻的筛选确认和产物的检测过程：
挑取10个左右含有25ug/mL氯霉素BG11固体培养基上长出来的单克隆蓝藻菌斑，接入5mL 25ug/mL氯霉素BG11液体体培养基中培养，待蓝藻培养好后，提取基因组，以设计好的引物PCR验证CHS和4CL两个目的基因，并PCR将产物送测序，确定基因序列是否正确；将验证正确的转CHS基因和4CL基因的Syn7942蓝藻接入100mL BG11液体培养基中光照培养，待OD730为1时，添加底物对羟基苯丙酸，同时添加IPTG诱导CHS和4CL两个基因表达，然后分别取诱导后培养1天、3天、5天时的转基因蓝藻，用高压破碎仪破碎蓝藻细胞，对产物分离提纯后，用高效液相色谱仪检测。
实施例四
本实施例提供根皮素的合成：
如附图4所示，在Syn7942细胞里外源表达4香豆酸-辅酶A连接酶（4 coumarateCoenzyme A Ligase， 4CL）和查尔酮合成酶（Chalcone synthase， CHS）这两个根皮素合成关键酶，以对羟基苯丙酸（或称根皮酸）为底物来催化生成根皮素，4CL催化一分子对羟基苯丙酸生成对羟基苯丙酰辅酶A，然后CHS催化3个分子的丙二酰辅酶A（malonyl coA）与一分子对羟基苯丙酰辅酶A合成一分子根皮素。
以上实验均用野生型Syn7942做阴性对照，其中对照组的根皮素液相图如图5所示，实施例中的液相结果、质谱结果如附图6-7所示，根据图5可以得出，野生型Syn7942做根皮素产物检测，没有峰图出现，说明其不产出根皮素，而根据图6所示，本实施例中的转基因Syn7942有根皮素峰图出现，说明有可能产根皮素，还需要进一步用质谱来确认产物就是根皮素，其中，根皮素分子量为274.27，而由图7可以看到产物中有一个275左右的峰出现，可以确认该产物就是根皮素，由此证明本实施例中公开的转基因Syn7942具有生产根皮素的效果，且该过程绿色环保低成本。
相关基因和氨基酸序列
Syn7942的NSI基因序列：
tatcaagattgctggggaagaaccgaccatccacaacgcgatcgagcggctgcttggcaaaaaccgtaaggaaatcgagcaaattgccaaggagaccctcgaaggcaacttgcgtggtgttttagccagcctcacgccggagcagatcaacgaggacaaaattgcctttgccaaaagtctgctggaagaggcggaggatgaccttgagcagctgggtctagtcctcgatacgctgcaagtccagaacatttccgatgaggtcggttatctctcggctagtggacgcaagcagcgggctgatctgcagcgagatgcccgaattgctgaagccgatgcccaggctgcctctgcgatccaaacggccgaaaatgacaagatcacggccctgcgtcggatcgatcgcgatgtagcgatcgcccaagccgaggccgagcgccggattcaggatgcgttgacgcggcgcgaagcggtggtggccgaagctgaagcggacattgctaccgaagtcgctcgtagccaagcagaactccctgtgcagcaggagcggatcaaacaggtgcagcagcaacttcaagccgatgtgatcgccccagctgaggcagcttgtaaacgggcgatcgcggaagcgcggggggccgccgcccgtatcgtcgaagatggaaaagctcaagcggaagggacccaacggctggcggaggcttggcagaccgctggtgctaatgcccgcgacatcttcctgctccagaagctcgagtccctgctcgtcacgctttcaggcaccgtgccagatatcgacgtggagtcgatcactgtgattggcgaaggggaaggcagcgctacccaaatcgctagcttgctggagaagctgaaacaaaccacgggcattgatctggcgaaatccctaccgggtcaatccgactcgcccgctgcgaagtcctaagagatagcgatgtgaccgcgatcgcttgtcaagaatcccagtgatcccgaaccataggaaggcaagctcaatgcttgcctcgtcttgaggactatctagatgtctgtggaacgcacatttattgccatcaagcccgatggcgttcagcggggtttggtcggtacgatcatcggccgctttgagcaaaaaggcttcaaactggtgggcctaaagcagctgaagcccagtcgcgagctggccgaacagcactatgctgtccaccgcgagcgccccttcttcaatggcctcgtcgagttcatcacctctgggccgatcgtggcgatcgtcttggaaggcgaaggcgttgtggcggctgctcgcaagttgatcggcgctaccaatccgctgacggcagaaccgggcaccatccgtggtgattttggtgtcaatattggccgcaacatcatccatggctcggatgcaatcgaaacagcacaacaggaaattgctctctggtttagcccagcagagctaagtgattggacccccacgattcaaccctggctgtacgaataaggtctgcattccttcagagagacattgccatgcc
氨基酸序列
4CL：
<110> 嘉兴欣贝莱生物科技有限公司
<120> 根皮素的一种合成路线
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<141> 2017-09-04
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<170> PatentIn version 3.3
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Ser Glu His Met Val Asp Leu Lys Glu Lys Phe Lys Arg Met Cys Asp
50 55 60
Lys Ser Met Ile Arg Lys Arg Tyr Met His Leu Thr Glu Glu Tyr Leu
65 70 75 80
Lys Glu Asn Pro Ser Leu Cys Glu Tyr Met Ala Pro Ser Leu Asp Ala
85 90 95
Arg Gln Asp Val Val Val Val Glu Val Pro Lys Leu Gly Lys Glu Ala
100 105 110
Ala Thr Lys Ala Ile Lys Glu Trp Gly Gln Pro Lys Ser Lys Ile Thr
115 120 125
His Leu Ile Phe Cys Thr Thr Ser Gly Val Asp Met Pro Gly Ala Asp
130 135 140
Tyr Gln Leu Thr Lys Leu Leu Gly Leu Arg Pro Ser Val Lys Arg Phe
145 150 155 160
Met Met Tyr Gln Gln Gly Cys Phe Ala Gly Gly Thr Val Leu Arg Leu
165 170 175
Ala Lys Asp Leu Ala Glu Asn Asn Lys Gly Ala Arg Val Leu Val Val
180 185 190
Cys Ser Glu Ile Thr Ala Val Thr Phe Arg Gly Pro Asn Asp Thr His
195 200 205
Leu Asp Ser Leu Val Gly Gln Ala Leu Phe Gly Asp Gly Ala Ala Ala
210 215 220
Val Ile Val Gly Ser Asp Pro Asp Leu Thr Thr Glu Arg Pro Leu Phe
225 230 235 240
Glu Met Ile Ser Ala Ala Gln Thr Ile Leu Pro Asp Ser Glu Gly Ala
245 250 255
Ile Asp Gly His Leu Arg Glu Val Gly Leu Thr Phe His Leu Leu Lys
260 265 270
Asp Val Pro Gly Leu Ile Ser Lys Asn Ile Glu Lys Ala Leu Thr Gln
275 280 285
Ala Phe Ser Pro Leu Gly Ile Ser Asp Trp Asn Ser Leu Phe Trp Ile
290 295 300
Ala His Pro Gly Gly Pro Ala Ile Leu Asp Gln Val Glu Leu Lys Leu
305 310 315 320
Gly Leu Lys Glu Glu Lys Met Arg Ala Thr Arg His Val Leu Ser Glu
325 330 335
Tyr Gly Asn Met Ser Ser Ala Cys Val Leu Phe Ile Ile Asp Glu Met
340 345 350
Arg Lys Lys Ser Ala Glu Asp Gly Ala Ala Thr Thr Gly Glu Gly Leu
355 360 365
Asp Trp Gly Val Leu Phe Gly Phe Gly Pro Gly Leu Thr Val Glu Thr
370 375 380
Val Val Leu His Ser Leu Pro Thr Thr Thr Ala Ile Ala Thr
385 390 395
Val Ile His Gly Ala Gln Ala Gly Gly Phe Ser Pro Ile Ser Ile Tyr
145 150 155
Gly Gly Ile Thr Asn Gln Ile Val Ala Lys Ala Gly Leu Pro Phe Ala
160 165 170 175
Pro Thr Ser Leu Phe Leu Ser Ser Phe Phe Phe Asn Leu Ala Ile Ala
180 185 190
Val Leu Val Phe Phe Val Phe Gly Gly Ala Arg Val Met Lys His Asp
195 200 205
Pro Ala Ser Leu Gly Pro Leu Pro Glu Leu His Pro Glu Gly Val Ser
210 215 220
Ala Ser Ile Arg Gly His Gly Gly Thr Pro Ala Lys Pro Ile Arg Glu
225 230 235
His Ala Tyr Gly Thr Ala Ala Asp Thr Ala Thr Thr Leu Arg Leu Asn
240 245 250 255
Asn Glu Arg Ile Thr Thr Leu Ile Gly Leu Thr Ala Leu Gly Ile Gly
260 265 270
Ala Leu Val Phe Lys Phe Asn Val Gly Leu Val Ala Met Thr Val Ala
275 280 285
Val Val Leu Ala Leu Leu Ser Pro Lys Thr Gln Lys Ala Ala Ile Asp
290 295 300
Lys Val Ser Trp Ser Thr Val Leu Leu Ile Ala Gly Ile Ile Thr Tyr
305 310 315
Val Gly Val Met Glu Lys Ala Gly Thr Val Asp Tyr Val Ala Asn Gly
320 325 330 335
Ile Ser Ser Leu Gly Met Pro Leu Leu Val Ala Leu Leu Leu Cys Phe
340 345 350
Thr Gly Ala Ile Val Ser Ala Phe Ala Ser Ser Thr Ala Leu Leu Gly
355 360 365
Ala Ile Ile Pro Leu Ala Val Pro Phe Leu Leu Gln Gly His Ile Ser
370 375 380
Ala Ile Gly Val Val Ala Ala Ile Ala Ile Ser Thr Thr Ile Val Asp
385 390 395
Thr Ser Pro Phe Ser Thr Asn Gly Ala Leu Val Val Ala Asn Ala Pro
400 405 410 415
Asp Asp Ser Arg Glu Gln Val Leu Arg Gln Leu Leu Ile Tyr Ser Ala
420 425 430
Leu Ile Ala Ile Ile Gly Pro Ile Val Ala Trp Leu Val Phe Val Val
435 440 445
Pro Gly Leu Val
450
综上所述，上述实施方式并非是本发明的限制性实施方式，凡本领域的技术人员在本发明的实质内容的基础上所进行的修饰或者等效变形，均在本发明的技术范畴。
Claims (7)
1.一种利用蓝藻合成根皮素的方法，其特征在于，将4香豆酸-辅酶A连接酶基因（4CL）以及查尔酮合成酶基因（CHS），导入蓝藻细胞得到重组蓝藻细胞，利用重组蓝藻细胞催化对羟基苯丙酸得到根皮素。
2.根据权利要求1所述的方法，其特征在于，所述蓝藻为聚球藻Synechococcuselongatus PCC7942。
3.根据权利要求2所述的方法，其特征在于，包括以下步骤： 构建整合载体NSI：选取所述Synechococcus elongatus PCC7942基因组上的基因序列段，且该段基因序列的改变不会影响Synechococcus elongatus PCC7942整个基因组的功能，以此来构建并获得整合载体NSI; 重组载体：根据Synechococcus elongatus PCC7942细胞密码子偏好性优化基因4CL和CHS的密码子，然后将这两个基因***到载体NSI上，得到带有氯霉素抗性基因的重组载体NSI-CHS-4CL； 同源重组：将重组载体NSI-CHS-4CL转化入Synechococcus elongatusPCC7942细胞内，通过同源重组作用，将CHS和4CL两个基因整合到Synechococcuselongatus PCC7942基因组上的NSI基因位点，并以诱导型启动子Trc来控制基因的表达；筛选确认：以氯霉素来筛选转化NSI-CHS-4CL载体后的Synechococcus elongatus PCC7942单克隆细胞，然后提取该细胞基因组，通过PCR分子鉴定试验确定最终携带有4CL基因和CHS基因的Synechococcus elongatus PCC7942； 催化合成：将经过筛选的Synechococcuselongatus PCC7942进行培养，添加底物对羟基苯丙酸，并添加IPTG诱导CHS和4CL两个基因表达，得到根皮素。
4.根据权利要求1-3任一项所述的方法，其特征在于，所述4CL根据向日葵中基因的氨基酸序列进行合成。
5.根据权利要求1-3任一项所述的方法，其特征在于，所述CHS根据灯盏花中基因的氨基酸序列进行合成。
6.根据权利要求3所述的方法，其特征在于，所述氯霉素筛选过程包括： S1：将同源重组后的细胞置于氯霉素固体培养基，初步筛选得到存活的Synechococcus elongatusPCC7942； S2：将所述Synechococcus elongatus PCC7942转接带有氯霉素抗性的液体培养基，待其成长后，提取其基因组，通过PCR分子鉴定试验确定最终携带有4CL基因和CHS基因的Synechococcus elongatus PCC7942。
7.根据权利要求3所述的方法，其特征在于，还包括：在催化合成根皮素之后，对收集完成的根皮素进行分离提纯，并利用高效液相色谱仪进行检测。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110960452A (zh) * | 2019-12-26 | 2020-04-07 | 嘉兴欣贝莱生物科技有限公司 | 一种含有根皮素的酵母浸出物及其制备工艺和应用 |
| CN112899314A (zh) * | 2021-02-04 | 2021-06-04 | 陕西师范大学 | 一种促进重组解脂亚罗酵母菌合成根皮素的方法 |
| CN114990086A (zh) * | 2022-06-16 | 2022-09-02 | 天津大学佐治亚理工深圳学院 | 酶组合物及其应用 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005084305A2 (en) * | 2004-03-01 | 2005-09-15 | Regents Of The University Of Minnesota | Flavonoids |
| US20070232495A1 (en) * | 2006-03-24 | 2007-10-04 | Nappa Alvaro O | Compositions and methods to add value to plant products, increasing the commercial quality, resistance to external factors and polyphenol content thereof |
| CN101748069A (zh) * | 2008-12-12 | 2010-06-23 | 中国科学院微生物研究所 | 一种重组蓝藻 |
| US20110093986A1 (en) * | 2008-06-26 | 2011-04-21 | Yeda Research And Development Co., Ltd At The Weizmann Institute Of Science | Tomato simyb12 transcription factor and genetic selection thereof |
| CN102978229A (zh) * | 2012-11-23 | 2013-03-20 | 中国科学院微生物研究所 | 蓝藻整合表达载体及其应用 |
| CN104726505A (zh) * | 2015-03-31 | 2015-06-24 | 上海交通大学 | 一种利用基因工程蓝藻生产三碳化合物的方法 |
| WO2016193504A1 (en) * | 2015-06-05 | 2016-12-08 | Evolva Sa | Biosynthesis of phenylpropanoid and dihydrophenylpropanoid derivatives |
| CN107805646A (zh) * | 2017-10-10 | 2018-03-16 | 嘉兴欣贝莱生物科技有限公司 | 一种大肠杆菌全细胞催化生产根皮素的方法 |
| CN107974484A (zh) * | 2017-11-10 | 2018-05-01 | 嘉兴欣贝莱生物科技有限公司 | 根皮素生物合成过程中查尔酮合成酶建模方法 |
-
2018
- 2018-06-05 CN CN201810566561.6A patent/CN109913508A/zh active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005084305A2 (en) * | 2004-03-01 | 2005-09-15 | Regents Of The University Of Minnesota | Flavonoids |
| US20050208643A1 (en) * | 2004-03-01 | 2005-09-22 | Claudia Schmidt-Dannert | Flavonoids |
| US20070232495A1 (en) * | 2006-03-24 | 2007-10-04 | Nappa Alvaro O | Compositions and methods to add value to plant products, increasing the commercial quality, resistance to external factors and polyphenol content thereof |
| US20110093986A1 (en) * | 2008-06-26 | 2011-04-21 | Yeda Research And Development Co., Ltd At The Weizmann Institute Of Science | Tomato simyb12 transcription factor and genetic selection thereof |
| CN101748069A (zh) * | 2008-12-12 | 2010-06-23 | 中国科学院微生物研究所 | 一种重组蓝藻 |
| CN102978229A (zh) * | 2012-11-23 | 2013-03-20 | 中国科学院微生物研究所 | 蓝藻整合表达载体及其应用 |
| CN104726505A (zh) * | 2015-03-31 | 2015-06-24 | 上海交通大学 | 一种利用基因工程蓝藻生产三碳化合物的方法 |
| WO2016193504A1 (en) * | 2015-06-05 | 2016-12-08 | Evolva Sa | Biosynthesis of phenylpropanoid and dihydrophenylpropanoid derivatives |
| CN107805646A (zh) * | 2017-10-10 | 2018-03-16 | 嘉兴欣贝莱生物科技有限公司 | 一种大肠杆菌全细胞催化生产根皮素的方法 |
| CN107974484A (zh) * | 2017-11-10 | 2018-05-01 | 嘉兴欣贝莱生物科技有限公司 | 根皮素生物合成过程中查尔酮合成酶建模方法 |
Non-Patent Citations (2)
| Title |
|---|
| NCBI: "4-coumarate--CoA ligase 2-like [Helianthus annuus]", GENBANK, pages 021984256 - 3 * |
| 楼士林 等: "蓝藻基因表达载体***的构建和应用", 厦门大学学报, vol. 40, no. 2, pages 586 - 591 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110960452A (zh) * | 2019-12-26 | 2020-04-07 | 嘉兴欣贝莱生物科技有限公司 | 一种含有根皮素的酵母浸出物及其制备工艺和应用 |
| CN112899314A (zh) * | 2021-02-04 | 2021-06-04 | 陕西师范大学 | 一种促进重组解脂亚罗酵母菌合成根皮素的方法 |
| CN112899314B (zh) * | 2021-02-04 | 2022-06-17 | 陕西师范大学 | 一种促进重组解脂亚罗酵母菌合成根皮素的方法 |
| CN114990086A (zh) * | 2022-06-16 | 2022-09-02 | 天津大学佐治亚理工深圳学院 | 酶组合物及其应用 |
| CN114990086B (zh) * | 2022-06-16 | 2024-05-07 | 天津大学佐治亚理工深圳学院 | 酶组合物及其应用 |
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