合成生物学 ›› 2021, Vol. 2 ›› Issue (2): 145-160.DOI: 10.12211/2096-8280.2020-052
张媛媛1, 曾艳2, 王钦宏1
收稿日期:
2020-06-07
修回日期:
2021-02-04
出版日期:
2021-04-30
发布日期:
2021-04-30
通讯作者:
王钦宏
作者简介:
基金资助:
ZHANG Yuanyuan1, ZENG Yan2, WANG Qinhong1
Received:
2020-06-07
Revised:
2021-02-04
Online:
2021-04-30
Published:
2021-04-30
Contact:
WANG Qinhong
摘要:
合成生物制造是以合成生物为工具进行物质加工与合成的生产方式,有望彻底变革未来医药、化工、食品、能源、材料、农业等传统模式,触发新的产业变革,引领新的产业模式和经济形态,重塑碳基物质文明。合成生物制造具有清洁、高效、可再生等特点,能够减少工业经济对生态环境的影响。本文综述了近年来合成生物制造在大宗发酵产品、精细与医药化学品、可再生化学品与聚合材料、天然产物、未来农产品以及一碳原料利用方面的重要进展,对各领域代表性重大产品的技术进展及产业应用状况与潜力进行了探讨。未来,随着合成生物学发展,以及与人工智能、大数据等新技术的融合,通过合成生物制造可以获得更多的生物基产品,促进生物经济形成,更好地服务于人类社会的可持续发展。
中图分类号:
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.
ZHANG Yuanyuan, ZENG Yan, WANG Qinhong. Advances in synthetic biomanufacturing[J]. Synthetic Biology Journal, 2021, 2(2): 145-160.
图1 合成生物制造示意图[Synthetic biomanufacturing is the new paradigm for material processing and synthesis via synthetic biology. Many bulk and fine chemicals, drugs, food, biofuels, and bio-based materials could be produce from renewable feedstocks, such as sugar, starch, cellulose, and even carbon-containing gases (CH4 , CO and CO2), via synthetic organisms as tools. Synthetic biomanufacturing is clean, efficient, and renewable, which can significantly reduce the impacts of industrial economy on the ecological environment. It is expected to revolutionize traditional industry and reshape the development of carbon-based civilization]
Fig. 1 Schematic diagram for synthetic biomanufacturing
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 | [ |
表1 芳香族化合物合成生物制造新进展
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 | [ |
表2 我国天然产物合成生物制造进展
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 | [ |
图2 未来农产品合成生物制造(With the help of sophisticated engineering strategies and tapping into vast resources in engineered strains, novel solutions for producing healthy sugar, animal-free milk, meat, and egg, synthetic starch and oil have already been developed and are getting close to moving from laboratory research to commercialization. Synthetic biomanufacturing of future food is revolutionizing the traditional food acquisition, processing and production mode, which is expected to provide adequate nourishment to billions of people)
Fig. 2 Schematic diagram for synthetic biomanufacturing of future food
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