Synthetic Biology Journal ›› 2020, Vol. 1 ›› Issue (3): 337-357.DOI: 10.12211/2096-8280.2020-014
• Invited Review • Previous Articles Next Articles
NIU Fuxing1, DU Yunping2, HUANG Yuanbin1, ZHOU Hetian2, LIU Jianzhong1
Received:
2020-03-02
Revised:
2020-04-14
Online:
2020-09-29
Published:
2020-06-30
Contact:
LIU Jianzhong
牛福星1, 杜云平2, 黄远斌1, 周荷田2, 刘建忠1
通讯作者:
刘建忠
作者简介:
牛福星(1988—),男,博士,博士后。研究方向为微生物代谢工程与合成生物学。E-mail: niufx3@mail.sysu.edu.cn基金资助:
CLC Number:
NIU Fuxing, DU Yunping, HUANG Yuanbin, ZHOU Hetian, LIU Jianzhong. Recent advances in the production of phenylpropanoic acids and their derivatives by genetically engineered microorganisms[J]. Synthetic Biology Journal, 2020, 1(3): 337-357.
牛福星, 杜云平, 黄远斌, 周荷田, 刘建忠. 工程微生物合成苯丙酸类化合物及其衍生物的研究进展[J]. 合成生物学, 2020, 1(3): 337-357.
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URL: https://synbioj.cip.com.cn/EN/10.12211/2096-8280.2020-014
Fig. 1 The artificial biosynthetic pathway of phenylpropanoids and their derivatives Black: endogenous genes; Red: exogenous genes. PEP—phosphoenolpyruvate; E4P—D-erythrose 4-phosphate; DAHP—3-deoxy-D-arabino-heptulosonate-7-phosphate; L-Trp—L-tryptophan; PP—phenylpyruvate; 4HPP—4-hydroxyphenylpyruvate; L-Phe—L-phenylanine; L-Tyr—L-tyrosine; aroF/aroG/aroH—3-deoxy-D-arabino-heptulosonate-7-phosphate synthase genes; trpDE—anthranilate synthase genes; pheA/tyrA—chorismate mutase/prephenate dehydrogenase genes; ldhA—lactate dehydrogenase gene; d-ldh—D-lactate dehydrogenase gene; hpaBC—p-hydroxyphenylacetate 3-hydroxylase genes; RAS—rosmarinic acid synthase gene; PAL1—phenylalanine ammonia lyase gene; tal—tyrosine ammonia lyase gene; 4cl—4-coumaroyl-coenzyme A ligase gene; HST—hydroxycinnamate-CoA shikimate transferase; FDC1—ferulic acid decarboxylase 1 gene; pdc—p-coumaric acid decarboxylase gene; sam5—4-coumarate hydroxylase gene; com—caffeic acid methyltransferase gene; HQT—hydroxycinnamoyl-CoA quinate transferase gene; pad—phenolic acid decarboxylase; DCS—phenyldiketide-CoA synthase gene; CURS—curcumin synthase gene
产品 | 应用 | 宿主 | 表达基因 | 敲除/置换基因 | 基质 | 培养条件 | 产量 | 生产力 | 文献 |
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苯丙烯酸类化合物 | |||||||||
肉桂酸 | 杀菌剂、 除草剂、 香料、医 药中间体 | 大肠杆菌W3110 | 马里蒂姆链霉菌苯丙氨酸解氨酶基因pal; 内源磷酸-2-脱氢-3-脱氧庚酸醛缩酶反馈抑制抗性基因aroGfbr 、莽草酸脱氢酶基因ydiB、莽草酸激酶Ⅰ、分枝酸变位酶反馈抑制抗性基因pheAfbr 、葡萄糖激酶基因glk和UDP-吡喃半乳糖变位酶基因galP | PTS系统EⅡA组分蛋白基因crr、转录调控蛋白TyrR基因、分枝酸变位酶基因tyrA和丙酮酸激酶Ⅱ基因pykA | 葡萄糖 | 2 L罐 补料发酵 | 6.9g/L | 0.08 g/(L·h) | [ |
酿酒酵母 | 密码子优化的发光杆菌苯丙氨酸解氨酶基因pal | 苯丙酮酸脱羧酶基因ARO10、去反馈抑制分枝酸变位酶基因ARO7G141S 和磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO4K229L置换天然基因 | 葡萄糖 | 摇床发酵 | 37.9mg/L | 1.58 mg/(L·h) | [ | ||
苯乙烯 | 聚合物 合成 | 大肠杆菌 NST74(ATCC 31884) | 拟南芥苯丙氨酸解氨酶基因PAL2、酿酒酵母肉桂酸脱羧酶基因FDC1 | 葡萄糖 | 摇床发酵 | 260mg/L | 8.97 mg/(L·h) | [ | |
大肠杆菌 NST74 | 拟南芥苯丙氨酸解氨酶基因PAL2、酿酒酵母肉桂酸脱羧酶基因FDC1 | 葡萄糖 | 二(2-乙基己基)邻苯二甲酸酯原位萃取摇床发酵 | 836mg/L | [ | ||||
大肠杆菌BL21(DE3) | 拟南芥苯丙氨酸解氨酶基因PAL2、肉桂酸脱羧酶基因FDC1、内源ppsA 和tktA; 内源磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroF、分枝酸变位酶基因 pheA、转酮酶I基因和磷酸烯醇式丙酮酸合成酶基因ppsA | 葡萄糖 | 异丙酯 原位萃取摇床发酵 | 350mg/L | 7.29 mg/(L·h) | [ | |||
大肠杆菌W3110 | 马里蒂姆链霉菌苯丙氨酸解氨酶基因pal; 内源磷酸-2-脱氢-3-脱氧庚酸醛缩酶反馈抑制抗性基因aroGfbr 、莽草酸脱氢酶基因ydiB、莽草酸激酶I、分枝酸变位酶反馈抑制抗性基因pheAfbr 、葡萄糖激酶基因glk、UDP-吡喃半乳糖变位酶基因galP和酿酒酵母阿魏酸脱羧酶I基因FDC1 | PTS系统EⅡA组分蛋白基因crr、转录调控蛋白TyrR基因、邻氨基苯甲酸合酶基因trpE、分枝酸变位酶基因tyrA和丙酮酸激酶Ⅱ基因 | 葡萄糖 | 5 L罐原 位萃取、 气提补 料发酵 | 5.3g/L | 88.3 mg/(L·h) | [ | ||
间氟-DL-苯丙氨酸抗性酿酒酵母 | 拟南芥苯丙氨酸解氨酶基因PAL2 | 去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO4K229L置换天然苯丙酮酸脱羧酶基因ARO10 | 葡萄糖 | 摇床发酵 | 29mg/L | 0.6 mg/L | [ | ||
浅青紫链霉菌-浅青紫链霉菌 | 第一个菌:酿酒酵母阿魏酸脱羧酶I基因FDC1。 另一个菌:马里蒂姆链霉菌苯丙氨酸解氨酶基因encP | 葡萄糖 | 摇床 共培养 | 30mg/L | 0.18 mg/(L·h) | [ | |||
对香 豆酸 | 抗氧化剂、抗菌剂及合成黄酮、多酚和聚酮化合物的前体 | 酿酒酵母CEN. PK102-5B | 约翰逊黄杆菌酪氨酸解氨酶基因tal、内源分枝酸变位酶反馈抑制抗性基因ARO7fbr, 磷酸-2-脱氢-3-脱氧庚酸醛缩酶反馈抑制抗性基因ARO4fbr 和 大肠杆菌莽草酸激酶Ⅱ基因aroL | 苯丙酮酸脱羧酶基因ARO10和丙酮酸脱羧酶基因PDC5 | 葡萄糖 | 1L罐 补料发酵 | 1.9g/L | [ | |
拟南芥P450还原酶基因ATR2和肉桂酸羟化酶基因C4H、内源细胞色素b5基因CYB5、大肠杆菌莽草酸激 酶Ⅱ基因aroL、内源去反馈 抑制分枝酸变位酶基因ARO7G141S、去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO4K229L、五功能AROM蛋白基因ARO1、分枝酸合成酶基因ARO2、磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO3、苯甲酸酯脱水酶基因PHA2和苜蓿预苯酸脱氢酶基因PDH1 约翰逊黄杆菌酪氨酸解氨酶基因tal、拟南芥基因PAL2、短双歧杆菌磷酸酮醇酶基因xfpk和克氏梭菌磷酸转乙酰酶基因pta | 丙酮酸脱羧酶基因PDC5、苯丙酮酸脱羧酶基因ARO10、半乳糖/乳糖代谢调节蛋白GAL80基因、磷酸果糖激酶Ⅰ、Ⅱ基因PFK1、PFK2和丙酮酸基因Ⅰ基因PYK1的天然启动子分别置换成组蛋白脱乙酰酶SET3、细胞分裂蛋白CDC24和乙醛脱氢酶ALD5基因天然启动子 | 葡萄糖 | 1L罐 补料发酵 | 12.5g/L | 130.1 mg/(L h) | [ | |||
对羟基苯乙烯 | 聚合物 合成 | 大肠杆菌NST74 | 黏红酵母酪氨酸/苯丙氨酸解氨酶基因PAL和植物乳杆菌对香豆酸脱羧酶基因pdc | 葡萄糖 | 14L罐 补料发酵 | 0.4g/L | 0.007 g/(L·h) | [ | |
大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal和解淀粉芽孢杆菌酚酸脱羧酶基因pad | 转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 摇床发酵 | 355mg/L | 9.86 mg/(L·h) | [ | ||
白斑链 霉菌 | 斯氏链霉菌的酚酸脱羧酶基因pad | 葡萄糖 | 摇床发酵 | 273mg/L | [ | ||||
恶臭假 单胞菌 | 黏红酵母酪氨酸/苯丙氨酸解氨酶基因PAL和植物乳杆菌对香豆酸脱羧酶基因pdc | 阿魏酸辅酶A合成酶基因fcs | 葡萄糖 | 3L罐 补料发酵 | 17.6g/L | 约0.29 g/(L·h) | [ | ||
咖啡酸 | 抗氧化剂、抗菌剂、抗病毒剂、抗肿瘤剂、抗炎剂及药物 | 大肠杆菌BW25113 | 荚膜红细菌酪氨酸解氨酶基因tal、大肠杆菌的4-羟基苯乙酸3-羟化酶基因hpaBC、天然去反馈抑制分枝酸变位酶-磷酸烯醇式丙酮酸合成酶-转酮酶-去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-ppsA-tktA-aroGfbr) | 转录调控蛋白TyrR基因 | 葡萄糖 | 摇床发酵 | 50.2mg/L | 1.05 mg/(L·h) | [ |
大肠杆菌MG1655 | 黏红酵母酪氨酸解氨酶基因TAL,西班牙糖丝菌对香豆酸3-羟化酶基因sam5、天然RNA聚合酶alpha亚基rpoA14突变体 | 分枝酸变位酶基因pheA;β-半乳糖苷酶基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇;转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 2 L罐补 料发酵 | 106mg/L | 1.10 mg/(L·h) | [ | ||
大肠杆菌ATCC 31884 | 黏红酵母酪氨酸解氨酶基因TAL和大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC, 去反馈抑制分枝酸变位酶-磷酸烯醇式丙酮酸合成酶-转酮酶-去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-ppsA-tktA-aroGfbr) | 分枝酸变位酶基因pheLA-tyrA | 葡萄糖 | 摇床发酵 | 766.68 mg/L | 10.65 mg/(L·h) | [ | ||
酿酒酵母 | 圆红冬孢酵母菌酪氨酸解氨酶基因TAL,铜绿假单胞菌4-羟基苯乙酸3-单加氧酶基因hpaB,肠道沙门菌NADPH-黄素氧化酶基因hpaC | 葡萄糖 | 摇床发酵 | 289.4 mg/L | 3.01 mg/(L·h) | [ | |||
绿原酸 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗炎剂 及药物 | 大肠杆菌BL21(DE3) | 烟草羟基肉桂酸辅酶A奎宁酸转移酶基因HQT、水稻对香豆酸辅酶A连接酶基因4CL和内源莽草酸/奎宁酸脱氢酶基因ydiB | 3-脱氢奎宁脱水酶基因aroD | 咖啡酸 | 摇床发酵 | 450mg/L | 18.75 mg/(L·h) | [ |
大肠杆菌-大肠杆菌 | 咖啡酸产生菌:西班牙糖丝菌酪氨酸解氨酶基因tal,天然磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroG和分枝酸变位酶基因tyrA,4-羟基苯乙酸3-羟化酶基因hpaBC 绿原酸产生菌:烟草羟基肉桂酸辅酶A奎宁酸转移酶基因HQT、水稻对香豆酸辅酶A连接酶基因4CL和内源莽草酸/奎宁酸脱氢酶基因ydiB | 咖啡酸产生菌:转录调控蛋白TyrR基因和分枝酸变位酶基因pheA | 葡萄糖 | 摇床共 培养 | 78mg/L | 1.44 mg/(L·h) | [ | ||
绿原酸产生菌:3-脱氢奎宁脱水酶基因aroD | |||||||||
对香豆酸-莽草酸酯 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗炎剂 及药物 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal,天然磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroG和分枝酸变位酶基因tyrA、烟草羟基肉桂酸辅酶A奎宁酸转移酶基因HQT、水稻对香豆酸辅酶A连接酶基因4CL | 转录调控蛋白TyrR基因、分枝酸变位酶基因pheA和莽草酸激酶II基因aroL | 葡萄糖 | 摇床发酵 | 236mg/L | 4.9 mg/(L·h) | [ |
3, 4-二羟基苯乙烯 | 聚合物合成 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal和对香豆酸3-羟化酶基因sam5、解淀粉芽孢杆菌酚酸脱羧酶基因pad | 转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 摇床发酵 | 63mg/L | 1.75 mg/(L·h) | [ |
阿魏酸 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗血栓剂 和心血管 药物 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal和对香豆酸3-羟化酶基因sam5、拟南芥O-甲基转移酶基因、天然去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 转录调控蛋白TyrR基因 | 葡萄糖 | 摇床发酵 | 196mg/L | 5.44 mg/(L·h) | [ |
大肠杆菌XL1-Blue | 简青霉的香草醇氧化酶基因vaoA、假单胞菌松柏醇脱氢酶基因calA及松柏醛脱氢酶基因calB | 丁香酚 | 30 L罐 补料发酵 | 14.7g/L | 0.49 g/(L·h) | [ | |||
姜黄素 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗炎剂,治疗帕金森病和阿尔茨海默病 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal、对香豆酸-3-羟化酶基因sam5、拟南芥O-甲基转移酶基因com、由烟草对香豆酸辅酶A连接酶基因4CL、姜黄苯二肽CoA合成酶基因DCS和姜黄素合成酶基因CURS2 | 转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 摇床发酵 | 3.8mg/L | [ | |
左旋 多巴 | 治疗帕 金森病 | 大肠杆菌W3110 | 去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 、转酮酶I基因tktA、对羟基苯乙酸3-羟化酶基因hpaBC、分枝酸变位酶结构域pheACM 和运动发酵单胞菌的环己二烯基脱氢酶基因tyrC | PTS 系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、乳糖抑制蛋白基因lacI和β-半乳糖苷酶基因;UDP-吡喃半乳糖变位酶基因galP的天然启动子置换成Ptrc 启动子 | 葡萄糖 | 摇床发酵 | 1.51g/L | 0.03 g/(L·h) | [ |
大肠杆菌BW25113 | 去反馈抑制分枝酸变位酶基因tyrAfbr 、芳香氨基酸转氨酶基因tyrB和4-羟基苯乙酸3-羟化酶基因hpaBC | 转录调控蛋白TyrR基因、PTS 系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、6-磷酸葡萄糖脱氢酶基因zwf和分枝酸变位酶基因pheLA;UDP-吡喃半乳糖变位酶基因galP和葡萄糖激酶基因glk | 葡萄糖 | 5 L罐 补料发酵 | 8.67g/L | 0.14 g/(L·h) | [ | ||
启动子置换成P37启动子; 去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 置换天然基因 | |||||||||
大肠杆菌W3110 | 4-羟基苯乙酸3-羟化酶基因hpaBC、芳香氨基酸转氨酶基因tyrB、分枝酸变位酶基因tyrA、分枝酸合成酶基因aroC、3-磷酸莽草酸1-羧酸乙烯基转移酶基因aroA和莽草酸激酶Ⅱ基因aroL | 转录调控蛋白TyrR基因、丙酮酸激酶Ⅰ基因pykF、3-磷酸甘油酸脱氢酶基因serA;去反馈抑制去磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 置换天然基因 | 葡萄糖 | 5 L罐 补料发酵 | 12.5g/L | [ | |||
大肠杆菌BL21 (DE3) | 4-羟基苯乙酸3-单加氧酶突变体基因hpaBG295R、NADPH-黄素氧化酶基因hpaC、UDP-吡喃半乳糖变位酶基因galP、葡萄糖激酶基因、磷酸烯醇式丙酮酸合酶基因ppsA、转酮酶Ⅰ基因tktA 、去反馈抑制去磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 和去反馈抑制分枝酸变位酶tyrAfbr | 转录调控蛋白TyrR基因、PTS 系统基因ptsG、PTS系统EIIA组分蛋白基因crr、分枝酸变位酶基因pheA和丙酮酸激酶Ⅰ基因pykF | 葡萄糖 | 5 L罐 补料发酵 | 25.53g/L | 0.53 g/(L·h) | [ | ||
苯乳酸类化合物 | |||||||||
L-苯 乳酸 | antioxidant,antifungal compound,synthesizing polymer | 大肠杆菌 | 植物乳杆菌乳酸脱氢酶基因L-ldh、巨大芽孢杆菌葡萄糖脱氢酶基因gdh | 苯丙酮酸(葡萄 糖供NADPH再生 之用) | 补料全细胞生物催化 | 103.8 mmol/L (17.25g/L) | 17.25 g/(L·h) | [ | |
植物乳杆菌乳酸脱氢酶基因L-ldh、奇异变形杆菌L-氨基酸解氨酶基因L-aad和博伊丁假丝酵母甲酸脱氢酶基因FDH | 苯丙氨酸(葡萄糖供辅因子再生用) | 摇床全细胞生物催化 | 54.0g/L | [ | |||||
大肠杆菌NST37 | 乳酸片球菌乳酸脱氢酶基因L-ldhA、天然去反馈抑制分枝酸变位酶基因pheAfbr 和去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr | 葡萄糖 | 摇床发酵 | 1.9g/L | 0.08 g/(L·h) | [ | |||
D-苯 乳酸 | 大肠杆菌NST37 | 荧光威克汉酵母苯丙酮酸还原酶基因pprA、天然去反馈抑制分枝酸变位酶基因pheAfbr 和去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr | 葡萄糖 | 0.4 L罐 补料发酵 | 29.2g/L | 0.20 g/(L·h) | [ | ||
4-羟基苯乳酸 | 抗氧化剂、抗菌剂和 聚合物合成 | 大肠杆菌BW25113(DE3) | 转录调控蛋白TyrR基因置换成去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶和分枝酸变位酶基因簇(aroFfbr-tyrAfbr );乙酰辅酶A合成酶基因置换成钩虫贪铜菌乳酸脱氢酶基因ldhA | 葡萄糖 | 摇床发酵 | 8.1 mmol/L | [ | ||
丹参素 | 抗氧化剂、抗肿瘤剂、抗炎剂及 其他药物 | 大肠杆菌BW25113 | 大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC、戊糖乳杆菌D-乳酸脱氢酶突变基因d-ldhY52A 、天然去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfb 、分枝酸变位酶基因tyrAfbr 、莽草酸脱氢酶基因aroE、磷酸烯醇式丙酮酸合酶基因ppsA、转酮酶Ⅰ基因tktA 和葡萄糖激酶基因glk | PTS系统基因ptsG、转录调控蛋白TyrR基因、丙酮酸激酶基因pykFA和分枝酸变位酶基因pheA | 葡萄糖 | 摇床补 料发酵 | 7.10g/L | 0.10 g/(L·h) | [ |
大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC、戊糖乳杆菌D-乳酸脱氢酶突变基因d-ldhY52A 、天然去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 、分枝酸变位酶基因tyrAfbr 、莽草酸脱氢酶基因aroE、磷酸烯醇式丙酮酸合酶基因ppsA、转酮酶Ⅰ基因tktA 和葡萄糖激酶基因glk | PTS系统基因ptsG、转录调控蛋白TyrR基因、丙酮酸激酶基因pykFA和分枝酸变位酶基因pheA | 葡萄糖 | 摇床补 料发酵 | 5.6g/L | 0.09 g/(L·h) | [ | |||
迷迭 香酸 | 抗氧化剂、抗菌剂、 抗肿瘤剂、抗炎剂和免疫调节剂 | 大肠杆菌-大肠杆菌-大肠杆菌 | 咖啡酸产生菌:黏红酵母酪氨酸解氨酶基因tal、4-羟基苯乙酸3-羟化酶基因hpaBC、莽草酸脱氢酶基因aroE、RNA聚合酶alpha亚基突变体基因rpoAmut 丹参素产生菌:莽草酸脱氢酶基因aroE、莽草酸激酶II基因aroL、3-磷酸莽草酸1-羧乙烯基转移酶基因aroA、分支酸合成酶基因aroC、去反馈抑制变位酶基因tyrAfbr 和去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr、大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC和戊糖乳杆菌D-乳酸脱氢酶突变基因d-ldhY52A 迷迭香酸产生菌: 薯蓣对香豆酸辅酶A连接酶基因4CL和香蜂草迷迭香酸合成酶基因RAS | 咖啡酸产生菌:分枝酸变位酶基因pheA、转录调控蛋白TyrR基因、PTS系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、莽草酸脱氢酶基因aroE和莽草酸/奎宁酸脱氢酶基因ydiB;β-半乳糖苷酶基因和转录调控蛋白TyrR基因同时置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) 丹参素产生菌:木糖异构酶基因xylA 迷迭香酸产生菌:分枝酸变位酶基因pheA、转录调控蛋白TyrR基因、PTS系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、莽草酸脱氢酶基因aroE和莽草酸/奎宁酸脱氢酶基因ydiB;β-半乳糖苷酶基因和转录调控蛋白TyrR基因同时置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖和木糖(3:2) | 摇床共 培养 | 172mg/L | [ | |
大肠杆菌 | 苜蓿中华根瘤菌聚磷酸激酶基因、约翰逊不动杆菌聚磷酸激酶基因、拟南芥对香豆酸辅酶A连接酶基因4CL和彩叶草迷迭香酸合酶基因 | 咖啡酸 | 无细胞 生物催化 | 320mg/L | 320.04 mg/(L·h) | [ | |||
Tab. 1 Representative microorganisms engineered for the production of phenylpropanoids and their derivatives
产品 | 应用 | 宿主 | 表达基因 | 敲除/置换基因 | 基质 | 培养条件 | 产量 | 生产力 | 文献 |
---|---|---|---|---|---|---|---|---|---|
苯丙烯酸类化合物 | |||||||||
肉桂酸 | 杀菌剂、 除草剂、 香料、医 药中间体 | 大肠杆菌W3110 | 马里蒂姆链霉菌苯丙氨酸解氨酶基因pal; 内源磷酸-2-脱氢-3-脱氧庚酸醛缩酶反馈抑制抗性基因aroGfbr 、莽草酸脱氢酶基因ydiB、莽草酸激酶Ⅰ、分枝酸变位酶反馈抑制抗性基因pheAfbr 、葡萄糖激酶基因glk和UDP-吡喃半乳糖变位酶基因galP | PTS系统EⅡA组分蛋白基因crr、转录调控蛋白TyrR基因、分枝酸变位酶基因tyrA和丙酮酸激酶Ⅱ基因pykA | 葡萄糖 | 2 L罐 补料发酵 | 6.9g/L | 0.08 g/(L·h) | [ |
酿酒酵母 | 密码子优化的发光杆菌苯丙氨酸解氨酶基因pal | 苯丙酮酸脱羧酶基因ARO10、去反馈抑制分枝酸变位酶基因ARO7G141S 和磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO4K229L置换天然基因 | 葡萄糖 | 摇床发酵 | 37.9mg/L | 1.58 mg/(L·h) | [ | ||
苯乙烯 | 聚合物 合成 | 大肠杆菌 NST74(ATCC 31884) | 拟南芥苯丙氨酸解氨酶基因PAL2、酿酒酵母肉桂酸脱羧酶基因FDC1 | 葡萄糖 | 摇床发酵 | 260mg/L | 8.97 mg/(L·h) | [ | |
大肠杆菌 NST74 | 拟南芥苯丙氨酸解氨酶基因PAL2、酿酒酵母肉桂酸脱羧酶基因FDC1 | 葡萄糖 | 二(2-乙基己基)邻苯二甲酸酯原位萃取摇床发酵 | 836mg/L | [ | ||||
大肠杆菌BL21(DE3) | 拟南芥苯丙氨酸解氨酶基因PAL2、肉桂酸脱羧酶基因FDC1、内源ppsA 和tktA; 内源磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroF、分枝酸变位酶基因 pheA、转酮酶I基因和磷酸烯醇式丙酮酸合成酶基因ppsA | 葡萄糖 | 异丙酯 原位萃取摇床发酵 | 350mg/L | 7.29 mg/(L·h) | [ | |||
大肠杆菌W3110 | 马里蒂姆链霉菌苯丙氨酸解氨酶基因pal; 内源磷酸-2-脱氢-3-脱氧庚酸醛缩酶反馈抑制抗性基因aroGfbr 、莽草酸脱氢酶基因ydiB、莽草酸激酶I、分枝酸变位酶反馈抑制抗性基因pheAfbr 、葡萄糖激酶基因glk、UDP-吡喃半乳糖变位酶基因galP和酿酒酵母阿魏酸脱羧酶I基因FDC1 | PTS系统EⅡA组分蛋白基因crr、转录调控蛋白TyrR基因、邻氨基苯甲酸合酶基因trpE、分枝酸变位酶基因tyrA和丙酮酸激酶Ⅱ基因 | 葡萄糖 | 5 L罐原 位萃取、 气提补 料发酵 | 5.3g/L | 88.3 mg/(L·h) | [ | ||
间氟-DL-苯丙氨酸抗性酿酒酵母 | 拟南芥苯丙氨酸解氨酶基因PAL2 | 去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO4K229L置换天然苯丙酮酸脱羧酶基因ARO10 | 葡萄糖 | 摇床发酵 | 29mg/L | 0.6 mg/L | [ | ||
浅青紫链霉菌-浅青紫链霉菌 | 第一个菌:酿酒酵母阿魏酸脱羧酶I基因FDC1。 另一个菌:马里蒂姆链霉菌苯丙氨酸解氨酶基因encP | 葡萄糖 | 摇床 共培养 | 30mg/L | 0.18 mg/(L·h) | [ | |||
对香 豆酸 | 抗氧化剂、抗菌剂及合成黄酮、多酚和聚酮化合物的前体 | 酿酒酵母CEN. PK102-5B | 约翰逊黄杆菌酪氨酸解氨酶基因tal、内源分枝酸变位酶反馈抑制抗性基因ARO7fbr, 磷酸-2-脱氢-3-脱氧庚酸醛缩酶反馈抑制抗性基因ARO4fbr 和 大肠杆菌莽草酸激酶Ⅱ基因aroL | 苯丙酮酸脱羧酶基因ARO10和丙酮酸脱羧酶基因PDC5 | 葡萄糖 | 1L罐 补料发酵 | 1.9g/L | [ | |
拟南芥P450还原酶基因ATR2和肉桂酸羟化酶基因C4H、内源细胞色素b5基因CYB5、大肠杆菌莽草酸激 酶Ⅱ基因aroL、内源去反馈 抑制分枝酸变位酶基因ARO7G141S、去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO4K229L、五功能AROM蛋白基因ARO1、分枝酸合成酶基因ARO2、磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因ARO3、苯甲酸酯脱水酶基因PHA2和苜蓿预苯酸脱氢酶基因PDH1 约翰逊黄杆菌酪氨酸解氨酶基因tal、拟南芥基因PAL2、短双歧杆菌磷酸酮醇酶基因xfpk和克氏梭菌磷酸转乙酰酶基因pta | 丙酮酸脱羧酶基因PDC5、苯丙酮酸脱羧酶基因ARO10、半乳糖/乳糖代谢调节蛋白GAL80基因、磷酸果糖激酶Ⅰ、Ⅱ基因PFK1、PFK2和丙酮酸基因Ⅰ基因PYK1的天然启动子分别置换成组蛋白脱乙酰酶SET3、细胞分裂蛋白CDC24和乙醛脱氢酶ALD5基因天然启动子 | 葡萄糖 | 1L罐 补料发酵 | 12.5g/L | 130.1 mg/(L h) | [ | |||
对羟基苯乙烯 | 聚合物 合成 | 大肠杆菌NST74 | 黏红酵母酪氨酸/苯丙氨酸解氨酶基因PAL和植物乳杆菌对香豆酸脱羧酶基因pdc | 葡萄糖 | 14L罐 补料发酵 | 0.4g/L | 0.007 g/(L·h) | [ | |
大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal和解淀粉芽孢杆菌酚酸脱羧酶基因pad | 转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 摇床发酵 | 355mg/L | 9.86 mg/(L·h) | [ | ||
白斑链 霉菌 | 斯氏链霉菌的酚酸脱羧酶基因pad | 葡萄糖 | 摇床发酵 | 273mg/L | [ | ||||
恶臭假 单胞菌 | 黏红酵母酪氨酸/苯丙氨酸解氨酶基因PAL和植物乳杆菌对香豆酸脱羧酶基因pdc | 阿魏酸辅酶A合成酶基因fcs | 葡萄糖 | 3L罐 补料发酵 | 17.6g/L | 约0.29 g/(L·h) | [ | ||
咖啡酸 | 抗氧化剂、抗菌剂、抗病毒剂、抗肿瘤剂、抗炎剂及药物 | 大肠杆菌BW25113 | 荚膜红细菌酪氨酸解氨酶基因tal、大肠杆菌的4-羟基苯乙酸3-羟化酶基因hpaBC、天然去反馈抑制分枝酸变位酶-磷酸烯醇式丙酮酸合成酶-转酮酶-去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-ppsA-tktA-aroGfbr) | 转录调控蛋白TyrR基因 | 葡萄糖 | 摇床发酵 | 50.2mg/L | 1.05 mg/(L·h) | [ |
大肠杆菌MG1655 | 黏红酵母酪氨酸解氨酶基因TAL,西班牙糖丝菌对香豆酸3-羟化酶基因sam5、天然RNA聚合酶alpha亚基rpoA14突变体 | 分枝酸变位酶基因pheA;β-半乳糖苷酶基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇;转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 2 L罐补 料发酵 | 106mg/L | 1.10 mg/(L·h) | [ | ||
大肠杆菌ATCC 31884 | 黏红酵母酪氨酸解氨酶基因TAL和大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC, 去反馈抑制分枝酸变位酶-磷酸烯醇式丙酮酸合成酶-转酮酶-去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-ppsA-tktA-aroGfbr) | 分枝酸变位酶基因pheLA-tyrA | 葡萄糖 | 摇床发酵 | 766.68 mg/L | 10.65 mg/(L·h) | [ | ||
酿酒酵母 | 圆红冬孢酵母菌酪氨酸解氨酶基因TAL,铜绿假单胞菌4-羟基苯乙酸3-单加氧酶基因hpaB,肠道沙门菌NADPH-黄素氧化酶基因hpaC | 葡萄糖 | 摇床发酵 | 289.4 mg/L | 3.01 mg/(L·h) | [ | |||
绿原酸 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗炎剂 及药物 | 大肠杆菌BL21(DE3) | 烟草羟基肉桂酸辅酶A奎宁酸转移酶基因HQT、水稻对香豆酸辅酶A连接酶基因4CL和内源莽草酸/奎宁酸脱氢酶基因ydiB | 3-脱氢奎宁脱水酶基因aroD | 咖啡酸 | 摇床发酵 | 450mg/L | 18.75 mg/(L·h) | [ |
大肠杆菌-大肠杆菌 | 咖啡酸产生菌:西班牙糖丝菌酪氨酸解氨酶基因tal,天然磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroG和分枝酸变位酶基因tyrA,4-羟基苯乙酸3-羟化酶基因hpaBC 绿原酸产生菌:烟草羟基肉桂酸辅酶A奎宁酸转移酶基因HQT、水稻对香豆酸辅酶A连接酶基因4CL和内源莽草酸/奎宁酸脱氢酶基因ydiB | 咖啡酸产生菌:转录调控蛋白TyrR基因和分枝酸变位酶基因pheA | 葡萄糖 | 摇床共 培养 | 78mg/L | 1.44 mg/(L·h) | [ | ||
绿原酸产生菌:3-脱氢奎宁脱水酶基因aroD | |||||||||
对香豆酸-莽草酸酯 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗炎剂 及药物 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal,天然磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroG和分枝酸变位酶基因tyrA、烟草羟基肉桂酸辅酶A奎宁酸转移酶基因HQT、水稻对香豆酸辅酶A连接酶基因4CL | 转录调控蛋白TyrR基因、分枝酸变位酶基因pheA和莽草酸激酶II基因aroL | 葡萄糖 | 摇床发酵 | 236mg/L | 4.9 mg/(L·h) | [ |
3, 4-二羟基苯乙烯 | 聚合物合成 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal和对香豆酸3-羟化酶基因sam5、解淀粉芽孢杆菌酚酸脱羧酶基因pad | 转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 摇床发酵 | 63mg/L | 1.75 mg/(L·h) | [ |
阿魏酸 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗血栓剂 和心血管 药物 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal和对香豆酸3-羟化酶基因sam5、拟南芥O-甲基转移酶基因、天然去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 转录调控蛋白TyrR基因 | 葡萄糖 | 摇床发酵 | 196mg/L | 5.44 mg/(L·h) | [ |
大肠杆菌XL1-Blue | 简青霉的香草醇氧化酶基因vaoA、假单胞菌松柏醇脱氢酶基因calA及松柏醛脱氢酶基因calB | 丁香酚 | 30 L罐 补料发酵 | 14.7g/L | 0.49 g/(L·h) | [ | |||
姜黄素 | 抗氧化剂、抗菌剂、 抗病毒剂、抗肿瘤剂、抗炎剂,治疗帕金森病和阿尔茨海默病 | 大肠杆菌 | 西班牙糖丝菌酪氨酸解氨酶基因tal、对香豆酸-3-羟化酶基因sam5、拟南芥O-甲基转移酶基因com、由烟草对香豆酸辅酶A连接酶基因4CL、姜黄苯二肽CoA合成酶基因DCS和姜黄素合成酶基因CURS2 | 转录调控蛋白TyrR基因置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖 | 摇床发酵 | 3.8mg/L | [ | |
左旋 多巴 | 治疗帕 金森病 | 大肠杆菌W3110 | 去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 、转酮酶I基因tktA、对羟基苯乙酸3-羟化酶基因hpaBC、分枝酸变位酶结构域pheACM 和运动发酵单胞菌的环己二烯基脱氢酶基因tyrC | PTS 系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、乳糖抑制蛋白基因lacI和β-半乳糖苷酶基因;UDP-吡喃半乳糖变位酶基因galP的天然启动子置换成Ptrc 启动子 | 葡萄糖 | 摇床发酵 | 1.51g/L | 0.03 g/(L·h) | [ |
大肠杆菌BW25113 | 去反馈抑制分枝酸变位酶基因tyrAfbr 、芳香氨基酸转氨酶基因tyrB和4-羟基苯乙酸3-羟化酶基因hpaBC | 转录调控蛋白TyrR基因、PTS 系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、6-磷酸葡萄糖脱氢酶基因zwf和分枝酸变位酶基因pheLA;UDP-吡喃半乳糖变位酶基因galP和葡萄糖激酶基因glk | 葡萄糖 | 5 L罐 补料发酵 | 8.67g/L | 0.14 g/(L·h) | [ | ||
启动子置换成P37启动子; 去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 置换天然基因 | |||||||||
大肠杆菌W3110 | 4-羟基苯乙酸3-羟化酶基因hpaBC、芳香氨基酸转氨酶基因tyrB、分枝酸变位酶基因tyrA、分枝酸合成酶基因aroC、3-磷酸莽草酸1-羧酸乙烯基转移酶基因aroA和莽草酸激酶Ⅱ基因aroL | 转录调控蛋白TyrR基因、丙酮酸激酶Ⅰ基因pykF、3-磷酸甘油酸脱氢酶基因serA;去反馈抑制去磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 置换天然基因 | 葡萄糖 | 5 L罐 补料发酵 | 12.5g/L | [ | |||
大肠杆菌BL21 (DE3) | 4-羟基苯乙酸3-单加氧酶突变体基因hpaBG295R、NADPH-黄素氧化酶基因hpaC、UDP-吡喃半乳糖变位酶基因galP、葡萄糖激酶基因、磷酸烯醇式丙酮酸合酶基因ppsA、转酮酶Ⅰ基因tktA 、去反馈抑制去磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 和去反馈抑制分枝酸变位酶tyrAfbr | 转录调控蛋白TyrR基因、PTS 系统基因ptsG、PTS系统EIIA组分蛋白基因crr、分枝酸变位酶基因pheA和丙酮酸激酶Ⅰ基因pykF | 葡萄糖 | 5 L罐 补料发酵 | 25.53g/L | 0.53 g/(L·h) | [ | ||
苯乳酸类化合物 | |||||||||
L-苯 乳酸 | antioxidant,antifungal compound,synthesizing polymer | 大肠杆菌 | 植物乳杆菌乳酸脱氢酶基因L-ldh、巨大芽孢杆菌葡萄糖脱氢酶基因gdh | 苯丙酮酸(葡萄 糖供NADPH再生 之用) | 补料全细胞生物催化 | 103.8 mmol/L (17.25g/L) | 17.25 g/(L·h) | [ | |
植物乳杆菌乳酸脱氢酶基因L-ldh、奇异变形杆菌L-氨基酸解氨酶基因L-aad和博伊丁假丝酵母甲酸脱氢酶基因FDH | 苯丙氨酸(葡萄糖供辅因子再生用) | 摇床全细胞生物催化 | 54.0g/L | [ | |||||
大肠杆菌NST37 | 乳酸片球菌乳酸脱氢酶基因L-ldhA、天然去反馈抑制分枝酸变位酶基因pheAfbr 和去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr | 葡萄糖 | 摇床发酵 | 1.9g/L | 0.08 g/(L·h) | [ | |||
D-苯 乳酸 | 大肠杆菌NST37 | 荧光威克汉酵母苯丙酮酸还原酶基因pprA、天然去反馈抑制分枝酸变位酶基因pheAfbr 和去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr | 葡萄糖 | 0.4 L罐 补料发酵 | 29.2g/L | 0.20 g/(L·h) | [ | ||
4-羟基苯乳酸 | 抗氧化剂、抗菌剂和 聚合物合成 | 大肠杆菌BW25113(DE3) | 转录调控蛋白TyrR基因置换成去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶和分枝酸变位酶基因簇(aroFfbr-tyrAfbr );乙酰辅酶A合成酶基因置换成钩虫贪铜菌乳酸脱氢酶基因ldhA | 葡萄糖 | 摇床发酵 | 8.1 mmol/L | [ | ||
丹参素 | 抗氧化剂、抗肿瘤剂、抗炎剂及 其他药物 | 大肠杆菌BW25113 | 大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC、戊糖乳杆菌D-乳酸脱氢酶突变基因d-ldhY52A 、天然去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfb 、分枝酸变位酶基因tyrAfbr 、莽草酸脱氢酶基因aroE、磷酸烯醇式丙酮酸合酶基因ppsA、转酮酶Ⅰ基因tktA 和葡萄糖激酶基因glk | PTS系统基因ptsG、转录调控蛋白TyrR基因、丙酮酸激酶基因pykFA和分枝酸变位酶基因pheA | 葡萄糖 | 摇床补 料发酵 | 7.10g/L | 0.10 g/(L·h) | [ |
大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC、戊糖乳杆菌D-乳酸脱氢酶突变基因d-ldhY52A 、天然去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr 、分枝酸变位酶基因tyrAfbr 、莽草酸脱氢酶基因aroE、磷酸烯醇式丙酮酸合酶基因ppsA、转酮酶Ⅰ基因tktA 和葡萄糖激酶基因glk | PTS系统基因ptsG、转录调控蛋白TyrR基因、丙酮酸激酶基因pykFA和分枝酸变位酶基因pheA | 葡萄糖 | 摇床补 料发酵 | 5.6g/L | 0.09 g/(L·h) | [ | |||
迷迭 香酸 | 抗氧化剂、抗菌剂、 抗肿瘤剂、抗炎剂和免疫调节剂 | 大肠杆菌-大肠杆菌-大肠杆菌 | 咖啡酸产生菌:黏红酵母酪氨酸解氨酶基因tal、4-羟基苯乙酸3-羟化酶基因hpaBC、莽草酸脱氢酶基因aroE、RNA聚合酶alpha亚基突变体基因rpoAmut 丹参素产生菌:莽草酸脱氢酶基因aroE、莽草酸激酶II基因aroL、3-磷酸莽草酸1-羧乙烯基转移酶基因aroA、分支酸合成酶基因aroC、去反馈抑制变位酶基因tyrAfbr 和去反馈抑制磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因aroGfbr、大肠杆菌4-羟基苯乙酸3-羟化酶基因hpaBC和戊糖乳杆菌D-乳酸脱氢酶突变基因d-ldhY52A 迷迭香酸产生菌: 薯蓣对香豆酸辅酶A连接酶基因4CL和香蜂草迷迭香酸合成酶基因RAS | 咖啡酸产生菌:分枝酸变位酶基因pheA、转录调控蛋白TyrR基因、PTS系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、莽草酸脱氢酶基因aroE和莽草酸/奎宁酸脱氢酶基因ydiB;β-半乳糖苷酶基因和转录调控蛋白TyrR基因同时置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) 丹参素产生菌:木糖异构酶基因xylA 迷迭香酸产生菌:分枝酸变位酶基因pheA、转录调控蛋白TyrR基因、PTS系统基因ptsIH、PTS系统EIIA组分蛋白基因crr、莽草酸脱氢酶基因aroE和莽草酸/奎宁酸脱氢酶基因ydiB;β-半乳糖苷酶基因和转录调控蛋白TyrR基因同时置换成去反馈抑制分枝酸变位酶-磷酸-2-脱氢-3-脱氧庚酸醛缩酶基因簇(tyrAfbr-aroGfbr ) | 葡萄糖和木糖(3:2) | 摇床共 培养 | 172mg/L | [ | |
大肠杆菌 | 苜蓿中华根瘤菌聚磷酸激酶基因、约翰逊不动杆菌聚磷酸激酶基因、拟南芥对香豆酸辅酶A连接酶基因4CL和彩叶草迷迭香酸合酶基因 | 咖啡酸 | 无细胞 生物催化 | 320mg/L | 320.04 mg/(L·h) | [ | |||
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