合成生物学 ›› 2025, Vol. 6 ›› Issue (5): 1145-1166.DOI: 10.12211/2096-8280.2025-082
李一塍, 罗会颖, 姚斌, 涂涛
收稿日期:2025-08-01
修回日期:2025-08-29
出版日期:2025-10-31
发布日期:2025-11-05
通讯作者:
涂涛
作者简介:基金资助:LI Yicheng, LUO Huiying, YAO Bin, TU Tao
Received:2025-08-01
Revised:2025-08-29
Online:2025-10-31
Published:2025-11-05
Contact:
TU Tao
摘要:
动物营养是保障畜牧业可持续发展的关键环节,动物营养过程的效率直接关系到资源利用效率、环境承载能力与粮食安全。随着农业合成生物技术的快速发展,研究者正积极应用工程化策略革新动物营养利用体系,主要涵盖饲料原料开发、饲料添加剂合成及胃肠道高效营养转化等方向。本文系统综述了该领域的最新进展,重点聚焦于基因编辑作物、微生物蛋白、饲料添加剂、胃肠道工程微生物等方向的关键使能技术与工程化策略,阐释了农业合成生物学在提升饲料利用效率、保障动物健康及促进畜牧业绿色转型中的巨大潜力。探讨了当前农业合成生物学在动物营养领域所面临的挑战与未来发展趋势,包括多基因系统设计与AI设计驱动生物育种进入4.0时代,动态调控系统开发与机器学习强化细胞工厂全局调控,多维度设计与学科交叉用于解析与调控动物消化系统。强调了其理念与技术对于突破现有技术瓶颈的关键作用。未来,农业合成生物学将通过深度融合多组学、机器学习与自动化平台技术,突破基因编辑与菌群调控难题,驱动动物营养创新发展。
中图分类号:
李一塍, 罗会颖, 姚斌, 涂涛. 农业合成生物学驱动动物营养创新:进展与展望[J]. 合成生物学, 2025, 6(5): 1145-1166.
LI Yicheng, LUO Huiying, YAO Bin, TU Tao. Agricultural synthetic biology driving innovation in animal nutrition: advances and prospects[J]. Synthetic Biology Journal, 2025, 6(5): 1145-1166.
| 微生物类型 | 菌种 | 底物 | 代谢途径 | 改造方法 | 产量/产率 | 产物 | 参考文献 |
|---|---|---|---|---|---|---|---|
| 甲基营养型酵母 | P. pastoris | 甲醇 | 氮代谢和细胞壁代谢 | 适应性实验室进化,过表达GDH1或GLN1 | 0.506 g/g DCW | 单细胞蛋白 | [ |
| 非天然甲基酵母 | Y. lipolytica | 甲醇 | RuMP和XuMP途径 | 引入RuMP和XuMP途径基因,敲除内源甲醛脱氢酶 | 1.1 g/L 72 h | 单细胞蛋白 | [ |
| 产乙酸菌 | A. woodii | 甲基、CO | 氢气利用途径 | 双敲除氢化酶hydBA/hdcr | — | 乳酸、单细胞蛋白 | [ |
| 天然甲酸利用菌 | P. communis | CO2 | — | 偶联电催化CO2还原模块与副球菌同化利用甲酸过程 | 2.6 g/L | 单细胞蛋白 | [ |
| 产乙酸菌 | Acetobacterium | CO2 | Wood-Ljungdahl途径 | 集成产乙酸菌利用CO2和产碱菌利用乙酸过程 | 1.5 g/(L·d) | 单细胞蛋白 | [ |
| 酵母 | S. cerevisiae | 玉米 秸秆 | — | 表面展示CBP和PGP | 3.23 g/L | 单细胞蛋白 | [ |
| R. toruloides | 玉米 秸秆 | — | 全过程设计预处理 | 蛋白208 g/kg 靛蓝素72 g/kg | 单细胞蛋白、靛蓝素 | [ | |
| C. utilisACCC 20060 | 棉花 秸秆 | — | 木糖利用微生物筛选 | 5.74 g/L | 单细胞蛋白 | [ |
表1 部分可合成单细胞蛋白的微生物
Table 1 Microorganisms capable to synthesize single-cell proteins
| 微生物类型 | 菌种 | 底物 | 代谢途径 | 改造方法 | 产量/产率 | 产物 | 参考文献 |
|---|---|---|---|---|---|---|---|
| 甲基营养型酵母 | P. pastoris | 甲醇 | 氮代谢和细胞壁代谢 | 适应性实验室进化,过表达GDH1或GLN1 | 0.506 g/g DCW | 单细胞蛋白 | [ |
| 非天然甲基酵母 | Y. lipolytica | 甲醇 | RuMP和XuMP途径 | 引入RuMP和XuMP途径基因,敲除内源甲醛脱氢酶 | 1.1 g/L 72 h | 单细胞蛋白 | [ |
| 产乙酸菌 | A. woodii | 甲基、CO | 氢气利用途径 | 双敲除氢化酶hydBA/hdcr | — | 乳酸、单细胞蛋白 | [ |
| 天然甲酸利用菌 | P. communis | CO2 | — | 偶联电催化CO2还原模块与副球菌同化利用甲酸过程 | 2.6 g/L | 单细胞蛋白 | [ |
| 产乙酸菌 | Acetobacterium | CO2 | Wood-Ljungdahl途径 | 集成产乙酸菌利用CO2和产碱菌利用乙酸过程 | 1.5 g/(L·d) | 单细胞蛋白 | [ |
| 酵母 | S. cerevisiae | 玉米 秸秆 | — | 表面展示CBP和PGP | 3.23 g/L | 单细胞蛋白 | [ |
| R. toruloides | 玉米 秸秆 | — | 全过程设计预处理 | 蛋白208 g/kg 靛蓝素72 g/kg | 单细胞蛋白、靛蓝素 | [ | |
| C. utilisACCC 20060 | 棉花 秸秆 | — | 木糖利用微生物筛选 | 5.74 g/L | 单细胞蛋白 | [ |
| 维生素 | 种类 | 改造方法 | 产量 | 参考文献 |
|---|---|---|---|---|
| 25(OH)VD3 | P450酶 | 嵌合型P450酶,全细胞催化 | 1.96 g/L | [ |
| VA | S. cerevisiae | 组合表达两种β-胡萝卜素裂解酶,引入视黄醇脱氢酶RDH12 | 5.21 g/L | [ |
| α-Tocotrienol | S. cerevisiae | 截短N端转运肽,解除限速步骤、增强前体供应,设计了冷休克触发温度控制系统 | 320 mg/L | [ |
| VB6 | E. coli | 解耦生长途径与生产途径,上游模块强化前体供应,下游模块改造限速酶 | 1409 mg/L | [ |
| VB5 | E. coli | 设计温度敏感开关动态调控细胞,精准分配碳通量,对关键酶进行理性改造 | 97.2 g/L | [ |
表2 代表性维生素及其衍生物的生物合成
Table 2 Biosynthesis of representative vitamins and their derivatives
| 维生素 | 种类 | 改造方法 | 产量 | 参考文献 |
|---|---|---|---|---|
| 25(OH)VD3 | P450酶 | 嵌合型P450酶,全细胞催化 | 1.96 g/L | [ |
| VA | S. cerevisiae | 组合表达两种β-胡萝卜素裂解酶,引入视黄醇脱氢酶RDH12 | 5.21 g/L | [ |
| α-Tocotrienol | S. cerevisiae | 截短N端转运肽,解除限速步骤、增强前体供应,设计了冷休克触发温度控制系统 | 320 mg/L | [ |
| VB6 | E. coli | 解耦生长途径与生产途径,上游模块强化前体供应,下游模块改造限速酶 | 1409 mg/L | [ |
| VB5 | E. coli | 设计温度敏感开关动态调控细胞,精准分配碳通量,对关键酶进行理性改造 | 97.2 g/L | [ |
| 氨基酸 | 菌株 | 改造策略 | 产量 | 参考文献 |
|---|---|---|---|---|
| L-赖氨酸 | C. glutamicum | 代谢工程重定向碳通量,并利用动态启动子库调控NADPH供应 | 223.4 g/L | [ |
| C. glutamicum | 关键酶改造、增加草酰乙酸和NADPH的供应及异源表达果糖激酶基因gmuE,提高生长速率 | 196.58 g/L | [ | |
| L-蛋氨酸 | E. coli | 增强琥珀酰辅酶A供应,引入直接硫磺酸化途径和削弱L-苏氨酸支链途径 | 20.39 g/L | [ |
| L-色氨酸 | E. coli | 优化了抗反馈酶AroG、TrpE和SerA的组合;敲入yddG和prsL135I,敲除poxB基因 | 43.0 g/L | [ |
| L-缬氨酸 | C. necator | 强化缬氨酸输出蛋白,敲除PHB合成途径,并筛选高效内源AHAS酶 | 972 mg/L | [ |
| L-异亮氨酸 | E. coli | 使用柠檬酸途径替代苏氨酸途径,同时强化DcuD转运蛋白并重构非氧化糖酵解途径 | 56.6 g/L | [ |
表3 代表性氨基酸的生物合成
Table 3 Biosynthesis of representative amino acids
| 氨基酸 | 菌株 | 改造策略 | 产量 | 参考文献 |
|---|---|---|---|---|
| L-赖氨酸 | C. glutamicum | 代谢工程重定向碳通量,并利用动态启动子库调控NADPH供应 | 223.4 g/L | [ |
| C. glutamicum | 关键酶改造、增加草酰乙酸和NADPH的供应及异源表达果糖激酶基因gmuE,提高生长速率 | 196.58 g/L | [ | |
| L-蛋氨酸 | E. coli | 增强琥珀酰辅酶A供应,引入直接硫磺酸化途径和削弱L-苏氨酸支链途径 | 20.39 g/L | [ |
| L-色氨酸 | E. coli | 优化了抗反馈酶AroG、TrpE和SerA的组合;敲入yddG和prsL135I,敲除poxB基因 | 43.0 g/L | [ |
| L-缬氨酸 | C. necator | 强化缬氨酸输出蛋白,敲除PHB合成途径,并筛选高效内源AHAS酶 | 972 mg/L | [ |
| L-异亮氨酸 | E. coli | 使用柠檬酸途径替代苏氨酸途径,同时强化DcuD转运蛋白并重构非氧化糖酵解途径 | 56.6 g/L | [ |
图5 农业合成生物学引导活性植物天然产物合成 [15](图5使用BioGDP.com制作)
Fig. 5 Agricultural synthetic biology drives active plant natural product synthesis [15](Fig. 5 was created with BioGDP.com)
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