CIESC Journal ›› 2020, Vol. 71 ›› Issue (9): 4058-4070.DOI: 10.11949/0438-1157.20200460
• Reviews and monographs • Previous Articles Next Articles
Hutao GAO(),Xiaolin SHEN,Xinxiao SUN,Jia WANG(),Qipeng YUAN()
Received:
2020-04-30
Revised:
2020-05-21
Online:
2020-09-05
Published:
2020-09-05
Contact:
Jia WANG,Qipeng YUAN
通讯作者:
王佳,袁其朋
作者简介:
高虎涛(1997—),男,硕士研究生,基金资助:
CLC Number:
Hutao GAO, Xiaolin SHEN, Xinxiao SUN, Jia WANG, Qipeng YUAN. Metabolic engineering strategies in biosynthesis of amino acids and their derivatives[J]. CIESC Journal, 2020, 71(9): 4058-4070.
高虎涛, 申晓林, 孙新晓, 王佳, 袁其朋. 代谢工程调控策略在生物合成氨基酸及其衍生物中的应用[J]. 化工学报, 2020, 71(9): 4058-4070.
Fig.1 Application of carbon source efficient utilization strategy(a) partial biosynthetic pathway of L-lysine in Corynebacterium glutamicum; (b) biosynthetic pathway of L-3,4-dihydroxyphenylalanine in E. coli;(c) biosynthetic pathway of S-adenosylmethionine in B. amyloliquefaciens; (d) biosynthetic pathway of 4-hydroxyisoleucine in E. coli
Fig.2 Application of speed-limiting step adjustment strategy(a) the metabolic pathway of homoserine production in E. coli; (b) the metabolic pathway of L-arginine in C. glutamicum; (c) the metabolic pathway of 5-hydroxytryptophan in E. coli
Fig.3 Application of carbon flux regulation strategy(a) the metabolic pathway of L-ornithine in C. glutamicum; (b) production and metabolism pathway of β-ornithine in E. coli
Fig.4 Application of transcription regulation and feedback inhibition regulation strategies(a) the metabolic pathway of 2-aminobutyric acid in E. coli; (b) L-leucine production and metabolic pathways in C. glutamicum
代谢工程策略 | 氨基酸及其衍生物 | 功能 | 工程菌 | 产量 | 文献 |
---|---|---|---|---|---|
碳源的高效利用 | 左旋鸟氨酸 | 一种非蛋白质氨基酸,能够加速伤口愈合并能有效维持心脏健康 | 谷氨酸棒状杆菌S9114 | 43.6 g/L | [ |
L-亮氨酸 | 在刺激肌肉蛋白质合成和葡萄糖稳态中具有重要作用 | 谷氨酸棒状杆菌 | 23.7 g/L | [ | |
L-赖氨酸 | 促进人体的发育、增强免疫力,并有提高中枢神经功能的作用 | 谷氨酸棒状杆菌 ZL-19 | 201.6 g/L | [ | |
L-3,4-二羟基苯丙氨酸 | 用于治疗帕金森氏疾病类药物的主要前体 | 大肠杆菌 | 1.51 g/L | [ | |
苯丙氨酸 | 用于生产人造甜味剂阿斯巴甜 | 大肠杆菌 | 1.4 g/L | [ | |
S-腺苷甲硫氨酸 | 被用作预防和治疗骨关节炎的功能性营养品或药物 | 解淀粉芽孢杆菌 | 107.47mg/L | [ | |
4-羟基异亮氨酸 | 在治疗和预防2-型糖尿病中有广阔应用前景 | 大肠杆菌 | 24.1 g/L | [ | |
限速步骤的调节 | 高丝氨酸 | 诱导免疫系统,增强植物对疾病的抵抗力 | 大肠杆菌W3110 | 1.20 g/L | [ |
L-高丙氨酸 | 抗癫痫药物左乙拉西坦和溴拉西坦的直接前体 | 大肠杆菌 | 5.4 g/L | [ | |
L-精氨酸 | 具有舒张因子的作用,临床上用于舒张和扩张血管 | 谷氨酸棒状杆菌 | 61.13 g/L | [ | |
L-赖氨酸 | 促进人体的发育、增强免疫力,并有提高中枢神经功能的作用 | 谷氨酸棒状杆菌 | 8.76 g/L | [ | |
5-羟基色氨酸 | 用于治疗和缓解抑郁症,有效治疗失眠和慢性头痛 | 大肠杆菌 | 1.11 g/L | [ | |
碳通量的调节 | L-鸟氨酸 | 用于治疗肝脏疾病和创伤,在肝脏保护中起着有效的作用 | 谷氨酸棒状杆菌 | 16 g/L | [ |
左旋肉碱 | 用于治疗功能障碍疾病 | 大肠杆菌 | 61.3 g/L | [ | |
β-丙氨酸 | 生物体中泛酸生产的主要前体 | 大肠杆菌 | 43.12 g/L | [ | |
5-氨基戊酸酯 | 生产尼龙的结构单元 | 谷氨酸棒状杆菌 | 28 g/L | [ | |
5-氨基乙酰丙酸 | 用于多种癌症的光动力学诊断和治疗中 | 谷氨酸棒状杆菌 | 2.06 g/L | [ | |
转录调节与反馈抑制调节 | L-酪氨酸 | 食品和饲料添加剂 | 酿酒酵母 | 36.2 mg/L | [ |
2-氨基丁酸 | 抗结核性乙胺丁醇的重要前体 | 大肠杆菌 | 5.39 g/L | [ | |
L-精氨酸 | 在食品和补充保健食品,制药和化妆品行业中有重要应用 | 谷氨酸棒状杆菌 | 61.9 g/L | [ | |
L-亮氨酸 | 在刺激肌肉蛋白质合成和葡萄糖稳态中具有重要作用 | 谷氨酸棒状杆菌 | 5.7 g/L | [ | |
L-苏氨酸 | 广泛用于食品、制药和化妆品行业 | 大肠杆菌 | 26.0 g/L | [ | |
转运系统的调节 | L-异亮氨酸 | 形成血红蛋白必需氨基酸,在调节血糖与能量方面起到关键作用 | 谷氨酸棒状杆菌 | 26.8 g/L | [ |
高丝氨酸 | 诱导免疫系统,增强植物对疾病的抵抗力 | 大肠杆菌W3110 | 39.54 g/L | [ | |
L-半胱氨酸 | 在提高动物的免疫调节和促进动物生长发育方面起着重要作用 | 大肠杆菌 | 634.4 mg/L | [ | |
L-蛋氨酸 | 用于脂肪肝,以及酒精等引起的肝损害 | 大肠杆菌 | 593.5 mg/L | [ | |
L-瓜氨酸 | 对于保持肌肉和肝脏健康有重要作用 | 谷氨酸棒状杆菌 | 21 g/L | [ | |
L-苏氨酸 | 促进人体发育和抗脂肪肝的药用效能 | 谷氨酸棒状杆菌 | 8.1 g/L | [ |
Table 1 Summary of amino acids and their derivatives involved in this article
代谢工程策略 | 氨基酸及其衍生物 | 功能 | 工程菌 | 产量 | 文献 |
---|---|---|---|---|---|
碳源的高效利用 | 左旋鸟氨酸 | 一种非蛋白质氨基酸,能够加速伤口愈合并能有效维持心脏健康 | 谷氨酸棒状杆菌S9114 | 43.6 g/L | [ |
L-亮氨酸 | 在刺激肌肉蛋白质合成和葡萄糖稳态中具有重要作用 | 谷氨酸棒状杆菌 | 23.7 g/L | [ | |
L-赖氨酸 | 促进人体的发育、增强免疫力,并有提高中枢神经功能的作用 | 谷氨酸棒状杆菌 ZL-19 | 201.6 g/L | [ | |
L-3,4-二羟基苯丙氨酸 | 用于治疗帕金森氏疾病类药物的主要前体 | 大肠杆菌 | 1.51 g/L | [ | |
苯丙氨酸 | 用于生产人造甜味剂阿斯巴甜 | 大肠杆菌 | 1.4 g/L | [ | |
S-腺苷甲硫氨酸 | 被用作预防和治疗骨关节炎的功能性营养品或药物 | 解淀粉芽孢杆菌 | 107.47mg/L | [ | |
4-羟基异亮氨酸 | 在治疗和预防2-型糖尿病中有广阔应用前景 | 大肠杆菌 | 24.1 g/L | [ | |
限速步骤的调节 | 高丝氨酸 | 诱导免疫系统,增强植物对疾病的抵抗力 | 大肠杆菌W3110 | 1.20 g/L | [ |
L-高丙氨酸 | 抗癫痫药物左乙拉西坦和溴拉西坦的直接前体 | 大肠杆菌 | 5.4 g/L | [ | |
L-精氨酸 | 具有舒张因子的作用,临床上用于舒张和扩张血管 | 谷氨酸棒状杆菌 | 61.13 g/L | [ | |
L-赖氨酸 | 促进人体的发育、增强免疫力,并有提高中枢神经功能的作用 | 谷氨酸棒状杆菌 | 8.76 g/L | [ | |
5-羟基色氨酸 | 用于治疗和缓解抑郁症,有效治疗失眠和慢性头痛 | 大肠杆菌 | 1.11 g/L | [ | |
碳通量的调节 | L-鸟氨酸 | 用于治疗肝脏疾病和创伤,在肝脏保护中起着有效的作用 | 谷氨酸棒状杆菌 | 16 g/L | [ |
左旋肉碱 | 用于治疗功能障碍疾病 | 大肠杆菌 | 61.3 g/L | [ | |
β-丙氨酸 | 生物体中泛酸生产的主要前体 | 大肠杆菌 | 43.12 g/L | [ | |
5-氨基戊酸酯 | 生产尼龙的结构单元 | 谷氨酸棒状杆菌 | 28 g/L | [ | |
5-氨基乙酰丙酸 | 用于多种癌症的光动力学诊断和治疗中 | 谷氨酸棒状杆菌 | 2.06 g/L | [ | |
转录调节与反馈抑制调节 | L-酪氨酸 | 食品和饲料添加剂 | 酿酒酵母 | 36.2 mg/L | [ |
2-氨基丁酸 | 抗结核性乙胺丁醇的重要前体 | 大肠杆菌 | 5.39 g/L | [ | |
L-精氨酸 | 在食品和补充保健食品,制药和化妆品行业中有重要应用 | 谷氨酸棒状杆菌 | 61.9 g/L | [ | |
L-亮氨酸 | 在刺激肌肉蛋白质合成和葡萄糖稳态中具有重要作用 | 谷氨酸棒状杆菌 | 5.7 g/L | [ | |
L-苏氨酸 | 广泛用于食品、制药和化妆品行业 | 大肠杆菌 | 26.0 g/L | [ | |
转运系统的调节 | L-异亮氨酸 | 形成血红蛋白必需氨基酸,在调节血糖与能量方面起到关键作用 | 谷氨酸棒状杆菌 | 26.8 g/L | [ |
高丝氨酸 | 诱导免疫系统,增强植物对疾病的抵抗力 | 大肠杆菌W3110 | 39.54 g/L | [ | |
L-半胱氨酸 | 在提高动物的免疫调节和促进动物生长发育方面起着重要作用 | 大肠杆菌 | 634.4 mg/L | [ | |
L-蛋氨酸 | 用于脂肪肝,以及酒精等引起的肝损害 | 大肠杆菌 | 593.5 mg/L | [ | |
L-瓜氨酸 | 对于保持肌肉和肝脏健康有重要作用 | 谷氨酸棒状杆菌 | 21 g/L | [ | |
L-苏氨酸 | 促进人体发育和抗脂肪肝的药用效能 | 谷氨酸棒状杆菌 | 8.1 g/L | [ |
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