Synthetic Biology Journal ›› 2021, Vol. 2 ›› Issue (6): 863-875.DOI: 10.12211/2096-8280.2021-015
• Invited Review • Previous Articles Next Articles
Xiaolong ZHANG1,2,3, Chenyun WANG1,2,3, Yanfeng LIU1,2,3, Jianghua LI2,3, Long LIU1,2,3, Guocheng DU1,2,3
Received:
2021-02-02
Revised:
2021-08-09
Online:
2022-01-21
Published:
2021-12-31
Contact:
Guocheng DU
张晓龙1,2,3, 王晨芸1,2,3, 刘延峰1,2,3, 李江华2,3, 刘龙1,2,3, 堵国成1,2,3
通讯作者:
堵国成
作者简介:
基金资助:
CLC Number:
Xiaolong ZHANG, Chenyun WANG, Yanfeng LIU, Jianghua LI, Long LIU, Guocheng DU. Research progress of constructing efficient biomanufacturing system based on synthetic biotechnology[J]. Synthetic Biology Journal, 2021, 2(6): 863-875.
张晓龙, 王晨芸, 刘延峰, 李江华, 刘龙, 堵国成. 基于合成生物技术构建高效生物制造系统的研究进展[J]. 合成生物学, 2021, 2(6): 863-875.
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URL: https://synbioj.cip.com.cn/EN/10.12211/2096-8280.2021-015
典型模式微生物 | 优缺点 | 适用范围 | 产品应用 |
---|---|---|---|
大肠杆菌 | 发酵周期短,遗传背景清晰,具有成熟的基因编辑工具以及多元化的代谢调控策略;但不适于表达需要翻译后修饰的蛋白及膜蛋白 | 非糖基化重组蛋白表达系统 | 类胡萝卜素、紫杉醇、青蒿酸、丹参素、1,3-丙二醇、1,4-丁二醇以及1,3-丁二醇 |
枯草芽孢杆菌 | 出色的蛋白质分泌系统;同时具有典型的芽孢形成能力、细胞分裂以及生物膜系统;但极易形成不溶性包涵体,潜在的脂多糖和内毒素风险 | 碱性丝氨酸蛋白酶与中温淀粉酶制备生产;为微生物机理研究的首选微生物之一 | 核苷酸、维生素、表面活性剂、维生素B2复合物、D-(-)-2,3-丁二醇、透明质酸[ |
地衣芽孢杆菌 | 清晰的遗传背景,出色的蛋白质分泌系统,在高温培养环境中拥有极佳的液化和糊化特性;但极易形成不溶性包涵体,潜在的脂多糖和内毒素风险 | 高温淀粉酶的工业化生产 | 耐热碱性蛋白酶、银纳米颗粒、生物絮凝剂、聚γ-谷氨酸、2,3-丁二醇 |
解淀粉芽孢杆菌 | 出色的蛋白质分泌系统;但极易形成不溶性包涵体,潜在的脂多糖和内毒素风险 | 中性或碱性蛋白酶的工业化生产 | 表面活性、果聚糖、S-腺苷甲硫氨酸、银纳米颗粒 |
谷氨酸棒杆菌 | 耗糖迅速,易于高密度发酵,无碳源分解代谢阻遏效应,且对有毒醇和芳香族化合物有较高耐受性;但遗传背景清晰,有成熟的调控工具 | 芳香族化合物的工业化生产 | L-谷氨酸、L-赖氨酸以及透明质酸 |
酿酒酵母 | 遗传背景清晰,胞内代谢机制高度解析,拥有内质网、线粒体等细胞器,且有较好的pH与渗透压耐受性;但其糖基化过高,较低的蛋白表达能力限制其工业化生产 | 适合生产生物能源、蛋白质、萜类、脂肪酸和脂肪醇、芳香族化合物等生物制品 | 乙酰辅酶A、香叶醇、柠檬烯、白藜芦醇、柚皮素、胰岛素等 |
巴斯德毕赤酵母 | 极佳的蛋白分泌能力,优异的翻译后修饰(糖基化与二硫键),并且胞外内源性蛋白极少 | 适合异源蛋白表达 | 人促红细胞生成素、磷脂酶C、人超氧化物歧化酶、胰蛋白酶、人血清白蛋白、胶原蛋白和人单克隆抗体3H6 Fab片段 |
Tab. 1 Summary of various typical model organism system and their scope of application
典型模式微生物 | 优缺点 | 适用范围 | 产品应用 |
---|---|---|---|
大肠杆菌 | 发酵周期短,遗传背景清晰,具有成熟的基因编辑工具以及多元化的代谢调控策略;但不适于表达需要翻译后修饰的蛋白及膜蛋白 | 非糖基化重组蛋白表达系统 | 类胡萝卜素、紫杉醇、青蒿酸、丹参素、1,3-丙二醇、1,4-丁二醇以及1,3-丁二醇 |
枯草芽孢杆菌 | 出色的蛋白质分泌系统;同时具有典型的芽孢形成能力、细胞分裂以及生物膜系统;但极易形成不溶性包涵体,潜在的脂多糖和内毒素风险 | 碱性丝氨酸蛋白酶与中温淀粉酶制备生产;为微生物机理研究的首选微生物之一 | 核苷酸、维生素、表面活性剂、维生素B2复合物、D-(-)-2,3-丁二醇、透明质酸[ |
地衣芽孢杆菌 | 清晰的遗传背景,出色的蛋白质分泌系统,在高温培养环境中拥有极佳的液化和糊化特性;但极易形成不溶性包涵体,潜在的脂多糖和内毒素风险 | 高温淀粉酶的工业化生产 | 耐热碱性蛋白酶、银纳米颗粒、生物絮凝剂、聚γ-谷氨酸、2,3-丁二醇 |
解淀粉芽孢杆菌 | 出色的蛋白质分泌系统;但极易形成不溶性包涵体,潜在的脂多糖和内毒素风险 | 中性或碱性蛋白酶的工业化生产 | 表面活性、果聚糖、S-腺苷甲硫氨酸、银纳米颗粒 |
谷氨酸棒杆菌 | 耗糖迅速,易于高密度发酵,无碳源分解代谢阻遏效应,且对有毒醇和芳香族化合物有较高耐受性;但遗传背景清晰,有成熟的调控工具 | 芳香族化合物的工业化生产 | L-谷氨酸、L-赖氨酸以及透明质酸 |
酿酒酵母 | 遗传背景清晰,胞内代谢机制高度解析,拥有内质网、线粒体等细胞器,且有较好的pH与渗透压耐受性;但其糖基化过高,较低的蛋白表达能力限制其工业化生产 | 适合生产生物能源、蛋白质、萜类、脂肪酸和脂肪醇、芳香族化合物等生物制品 | 乙酰辅酶A、香叶醇、柠檬烯、白藜芦醇、柚皮素、胰岛素等 |
巴斯德毕赤酵母 | 极佳的蛋白分泌能力,优异的翻译后修饰(糖基化与二硫键),并且胞外内源性蛋白极少 | 适合异源蛋白表达 | 人促红细胞生成素、磷脂酶C、人超氧化物歧化酶、胰蛋白酶、人血清白蛋白、胶原蛋白和人单克隆抗体3H6 Fab片段 |
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