Synthetic Biology Journal ›› 2021, Vol. 2 ›› Issue (2): 145-160.DOI: 10.12211/2096-8280.2020-052
• Invited Review • Previous Articles Next Articles
Yuanyuan ZHANG1, Yan ZENG2, Qinhong WANG1
Received:
2020-06-07
Revised:
2021-02-04
Online:
2021-04-30
Published:
2021-04-29
Contact:
Qinhong WANG
张媛媛1, 曾艳2, 王钦宏1
通讯作者:
王钦宏
作者简介:
基金资助:
CLC Number:
Yuanyuan ZHANG, Yan ZENG, Qinhong WANG. Advances in synthetic biomanufacturing[J]. Synthetic Biology Journal, 2021, 2(2): 145-160.
张媛媛, 曾艳, 王钦宏. 合成生物制造进展[J]. 合成生物学, 2021, 2(2): 145-160.
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URL: https://synbioj.cip.com.cn/EN/10.12211/2096-8280.2020-052
芳香族化合物 | 宿主细胞 | 发酵时间 | 发酵方式 | 产量 | 参考文献 |
---|---|---|---|---|---|
左旋多巴 | E. coli | 60 h | 分批补料发酵 | 57 g/L | [ |
羟基酪醇 | E. coli | 48 h | 摇瓶发酵 | 169.2 g /L | [ |
没食子酸 | E. coli | 48 h | 摇瓶发酵 | 1266.39 mg /L | [ |
水杨酸 | E. coli | 48 h | 分批补料发酵 | 11. 5 g /L | [ |
L-苯丙氨酸 | E. coli | 48 h | 分批补料发酵 | 72.9 g /L | [ |
苯乙醇 | E. coli | 72 h | 摇瓶发酵 | 3.59 g /L | [ |
肉桂酸 | E. coli | 80 h | 摇瓶发酵 | 1.7 g /L | [ |
L-色氨酸 | E. coli | 42 h | 分批补料发酵 | 39.7 g /L | [ |
香草醇 | E. coli | 36 h | 摇瓶发酵 | 240.69 mg /L | [ |
顺,顺黏康酸 | E. coli | 72 h | 分批补料发酵 | 64.5 g /L | [ |
Tab. 1 Progress of synthetic biomanufacturing of aromatic chemicals
芳香族化合物 | 宿主细胞 | 发酵时间 | 发酵方式 | 产量 | 参考文献 |
---|---|---|---|---|---|
左旋多巴 | E. coli | 60 h | 分批补料发酵 | 57 g/L | [ |
羟基酪醇 | E. coli | 48 h | 摇瓶发酵 | 169.2 g /L | [ |
没食子酸 | E. coli | 48 h | 摇瓶发酵 | 1266.39 mg /L | [ |
水杨酸 | E. coli | 48 h | 分批补料发酵 | 11. 5 g /L | [ |
L-苯丙氨酸 | E. coli | 48 h | 分批补料发酵 | 72.9 g /L | [ |
苯乙醇 | E. coli | 72 h | 摇瓶发酵 | 3.59 g /L | [ |
肉桂酸 | E. coli | 80 h | 摇瓶发酵 | 1.7 g /L | [ |
L-色氨酸 | E. coli | 42 h | 分批补料发酵 | 39.7 g /L | [ |
香草醇 | E. coli | 36 h | 摇瓶发酵 | 240.69 mg /L | [ |
顺,顺黏康酸 | E. coli | 72 h | 分批补料发酵 | 64.5 g /L | [ |
种类 | 天然产物 | 功效 | 改造策略 | 参考文献 |
---|---|---|---|---|
萜类 化合物 | β-胡萝卜素 | 抗氧化,免疫调节,抗癌等 | 通过导入β-胡萝卜素外源合成途径,并进行物质代谢、能量代谢、细胞生理调节优化改造,将其产量提高至2.1 g/L | [ |
番茄红素 | 抗氧化,保护心脑血管,增强免疫力 | 通过物质代谢、能量代谢、细胞生理调节等综合手段协同控制构建人工细胞,优化发酵过程,实现3.52 g/L或50.6 mg/g(以DCW计)的产量,正在进行产业化应用 | [ | |
丹参酮 | 抗氧化,抗菌,抗肿瘤等 | 通过构建含有关键基因CYP76AH1的铁锈醇高产酵母工程菌株,结合次丹参酮二烯合成功能酶以及P450基因,获得可同时生产多类型丹参酮化合物酵母工程菌株 | [ | |
齐墩果酸 | 抗菌药 | 对酿酒酵母进行分子改造等提升齐墩果酸的生物合成效率,结合发酵过程优化,最终实现产物浓度(606.9±9.1) mg/L及得率(16.0±0.8) mg/g (以DCW计),高出之前报道7.6倍 | [ | |
甘草次酸 | 抗炎及抗免疫等 | 在酿酒酵母中构建新型甘草次酸合成途径,实现产物甘草次酸浓度(18.9±2.0) mg/L,前体物11-氧代-β-糊精浓度(108.1±4.6) mg/L | [ | |
苯丙 素类 | 天麻素 | 神经衰弱及神经衰弱综合征 | 在国际上首次获得以葡萄糖为原料合成天麻素的高产人工细胞,发酵72 h,产量可达10 g/L,成本低于植物提取的1/200、化学合成的1/2,可替代化学合成 | [ |
红景天苷 | 抗缺氧、抗寒冷、抗病毒等 | 首次创建了红景天苷微生物异源高效合成新途径,以葡萄糖为原料,生产成本是植物提取的1/40、化学合成的1/10,具备了工业化应用潜力 | [ | |
灯盏乙素 | 治疗心脑血管疾病 | 理性设计灯盏乙素合成途径,筛选关键基因,以酿酒酵母为底盘细胞构建人工细胞,结合代谢调控、发酵过程优化,产量可达百毫克级,具有较好产业前景 | [ | |
丹参素 | 改善心血管疾病症状 | 构建了全新的生物合成途径,后期增强外源途径关键酶与底物的特异性提升丹参素产量,可达7 g/L,具有产业化应用前景 | [ |
Tab. 2 Progress of synthetic biomanufacturing of natural products in China
种类 | 天然产物 | 功效 | 改造策略 | 参考文献 |
---|---|---|---|---|
萜类 化合物 | β-胡萝卜素 | 抗氧化,免疫调节,抗癌等 | 通过导入β-胡萝卜素外源合成途径,并进行物质代谢、能量代谢、细胞生理调节优化改造,将其产量提高至2.1 g/L | [ |
番茄红素 | 抗氧化,保护心脑血管,增强免疫力 | 通过物质代谢、能量代谢、细胞生理调节等综合手段协同控制构建人工细胞,优化发酵过程,实现3.52 g/L或50.6 mg/g(以DCW计)的产量,正在进行产业化应用 | [ | |
丹参酮 | 抗氧化,抗菌,抗肿瘤等 | 通过构建含有关键基因CYP76AH1的铁锈醇高产酵母工程菌株,结合次丹参酮二烯合成功能酶以及P450基因,获得可同时生产多类型丹参酮化合物酵母工程菌株 | [ | |
齐墩果酸 | 抗菌药 | 对酿酒酵母进行分子改造等提升齐墩果酸的生物合成效率,结合发酵过程优化,最终实现产物浓度(606.9±9.1) mg/L及得率(16.0±0.8) mg/g (以DCW计),高出之前报道7.6倍 | [ | |
甘草次酸 | 抗炎及抗免疫等 | 在酿酒酵母中构建新型甘草次酸合成途径,实现产物甘草次酸浓度(18.9±2.0) mg/L,前体物11-氧代-β-糊精浓度(108.1±4.6) mg/L | [ | |
苯丙 素类 | 天麻素 | 神经衰弱及神经衰弱综合征 | 在国际上首次获得以葡萄糖为原料合成天麻素的高产人工细胞,发酵72 h,产量可达10 g/L,成本低于植物提取的1/200、化学合成的1/2,可替代化学合成 | [ |
红景天苷 | 抗缺氧、抗寒冷、抗病毒等 | 首次创建了红景天苷微生物异源高效合成新途径,以葡萄糖为原料,生产成本是植物提取的1/40、化学合成的1/10,具备了工业化应用潜力 | [ | |
灯盏乙素 | 治疗心脑血管疾病 | 理性设计灯盏乙素合成途径,筛选关键基因,以酿酒酵母为底盘细胞构建人工细胞,结合代谢调控、发酵过程优化,产量可达百毫克级,具有较好产业前景 | [ | |
丹参素 | 改善心血管疾病症状 | 构建了全新的生物合成途径,后期增强外源途径关键酶与底物的特异性提升丹参素产量,可达7 g/L,具有产业化应用前景 | [ |
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