生物法制造丁二酸研究进展

doi:10.11949/0438-1157.20191430

摘要/Abstract

摘要：

丁二酸因其C₄分子结构在化工领域的潜在价值，被认为是一种具有广阔应用前景的生物基平台化合物。结合生物基丁二酸的产业现状，综合分析了丁二酸生产菌种及菌株改造、生物过程优化和丁二酸分离纯化这三个方面的研究现状。重点介绍以大肠杆菌、产琥珀酸放线杆菌、解脂耶氏酵母为代表的主要生产菌株及其改造策略；低值生物质利用及控制发酵过程中CO₂ 供给和pH 调节等生物过程优化策略；包括钙盐法、电渗析法、直接分离法等方法在内的丁二酸分离工艺。同时指出未来的研究重点将综合考虑经济性与能耗问题，将菌株与发酵和分离全过程整合，提高丁二酸产量，降低发酵及分离成本，进一步拓展生物基丁二酸市场应用领域。

关键词: 丁二酸, 发酵, 生产菌株, 代谢工程, 生物过程, 下游过程

Abstract:

Succinic acid is considered to be a promising bio-based platform compound due to its potential value in the chemical industry for its C₄ molecular structure. This article comprehensively analyzed the domestic and foreign scholars research status of succinic acid in three aspects which were production strains and strain transformation, biological process optimization and separation process of succinic acid. It emphatically introduced the main production strains and their modification strategies, such as Escherichia coli, Actinobacillus succinogenes and Yarrowia lipolytica. It included the biological process optimization programs such as low biomass utilization, two stages and low pH fermentation strategy and CO₂ supply and pH regulation during fermentation. And it also included the separation process of succinic acid such as calcium salt method, electrodialysis method and direct separation method. At the same time, it pointed out that the emphasis of the future research will be to comprehensively consider the economic and energy consumption issues, integrate the whole process of strain fermentation and separation, increase the yield of succinic acid, reduce the cost of fermentation and separation and then to further expand the market of bio-based succinic acid.

Key words: succinic acid, fermentation, production strain, metabolic engineering, bioprocess, downstream process

中图分类号:

Q 599

张耀, 邱晓曼, 陈程鹏, 于卓然, 洪厚胜. 生物法制造丁二酸研究进展[J]. 化工学报, 2020, 71(5): 1964-1975.

Yao ZHANG, Xiaoman QIU, Chengpeng CHEN, Zhuoran YU, Housheng HONG. Recent progress in microbial production of succinic acid[J]. CIESC Journal, 2020, 71(5): 1964-1975.

图/表 4

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生产商	产能/(万吨/年)	原料	生产菌株	发酵及分离工艺
Myriant	1.4	糖浆/木质纤维素水解液	E. coli	氨水维持pH，氨沉淀法分离工艺
BioAmber	0.4	麦芽糖浆	E. coli	氢氧化钠维持pH，电透析法分离工艺
BioAmber & Mitsubishi	3.0	玉米糖浆	Candida krusei	低pH发酵，直接结晶工艺
Succinity	1.0	甘油/糖浆	Basfia succiniciproducens	Mg(OH)₂维持pH，镁盐分离工艺
Reverdia	1.0	糖浆	S. cerevisiae	低pH发酵，直接结晶工艺

生产商	产能/(万吨/年)	原料	生产菌株	发酵及分离工艺
Myriant	1.4	糖浆/木质纤维素水解液	E. coli	氨水维持pH，氨沉淀法分离工艺
BioAmber	0.4	麦芽糖浆	E. coli	氢氧化钠维持pH，电透析法分离工艺
BioAmber & Mitsubishi	3.0	玉米糖浆	Candida krusei	低pH发酵，直接结晶工艺
Succinity	1.0	甘油/糖浆	Basfia succiniciproducens	Mg(OH)₂维持pH，镁盐分离工艺
Reverdia	1.0	糖浆	S. cerevisiae	低pH发酵，直接结晶工艺

菌株	发酵方式	丁二酸产量/(g /L)	碳源	得率/(g/g)	生产速率/(g /( L·h))	Ref.
Y. lipolytica Y-3314	通氧	45.5	葡萄糖	-	-	[21]
Y. lipolytica PGC01003	通氧	160.2	粗甘油	0.40	0.40	[22]
Y. lipolytica PGC202	通氧；低pH	71.6	混合食物废弃物	0.61	0.40	[23]
S. cerevisiae	通氧	45.00	葡萄糖	-	0.45	[24]
A. succinogenes NJ113	厌氧	47.5	玉米芯水解液	0.68	0.63	[25]
A. succinogenes ATCC 55618	厌氧	151.44	木薯根水解液	1.51	3.22	[26]
E. coli YY-GS004	厌氧	57	甘油	1.28	0.59	[27]
E. coli AFP111	两阶段发酵	101.2	葡萄糖	1.1	1.3	[28]
E. coli Tang 1683	两阶段发酵	92.7	葡萄糖	0.73	1.25	[29]
C. glutamicum BOL-2	两阶段发酵	133.8	葡萄糖	1.10	2.48	[30]
C. glutamicum S071	厌氧	152.2	葡萄糖	1.10	1.11	[31]

菌株	发酵方式	丁二酸产量/(g /L)	碳源	得率/(g/g)	生产速率/(g /( L·h))	Ref.
Y. lipolytica Y-3314	通氧	45.5	葡萄糖	-	-	[21]
Y. lipolytica PGC01003	通氧	160.2	粗甘油	0.40	0.40	[22]
Y. lipolytica PGC202	通氧；低pH	71.6	混合食物废弃物	0.61	0.40	[23]
S. cerevisiae	通氧	45.00	葡萄糖	-	0.45	[24]
A. succinogenes NJ113	厌氧	47.5	玉米芯水解液	0.68	0.63	[25]
A. succinogenes ATCC 55618	厌氧	151.44	木薯根水解液	1.51	3.22	[26]
E. coli YY-GS004	厌氧	57	甘油	1.28	0.59	[27]
E. coli AFP111	两阶段发酵	101.2	葡萄糖	1.1	1.3	[28]
E. coli Tang 1683	两阶段发酵	92.7	葡萄糖	0.73	1.25	[29]
C. glutamicum BOL-2	两阶段发酵	133.8	葡萄糖	1.10	2.48	[30]
C. glutamicum S071	厌氧	152.2	葡萄糖	1.10	1.11	[31]

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