微生物合成二元醇研究进展

doi:10.12211/2096-8280.2024-014

摘要/Abstract

摘要：

二元醇是一类重要的大宗化学品，在高分子材料、化妆品、燃料、食品和制药行业中有着广泛应用。开发可利用生物质及碳一原料等可再生原料生产二元醇的生物合成路线对于降低化石资源依赖、减少二氧化碳的排放具有重要的意义，近年来受到了国内外广泛关注。虽然通过生物法生产1，3-丙二醇，1，3-丁二醇和1，4-丁二醇已实现商业化，但大多数其他二元醇的高效生物合成仍面临挑战，主要原因包括缺乏有效的天然生物合成途径、基因工程菌的产率低等。本综述全面探讨了微生物合成二元醇的最新研究进展，特别是在开发新代谢途径和代谢工程策略方面，以实现C2至C5二元醇的高效生物合成。例如通过对非天然合成途径的设计和构建以实现系列非天然二元醇的生物合成，以及利用非传统的碳源（如木质纤维素等）通过特定的代谢途径和优化策略合成二元醇，为生物合成领域开辟新的道路。此外，我们还讨论了这些生物合成过程向工业应用转化的主要挑战和未来的发展前景，包括廉价和可持续原料的获取、大规模放大过程的复杂性、满足下游特定需求的后提取工艺开发等。

关键词: 二元醇, 生物合成, 代谢工程, 可再生原料, 工业应用

Abstract:

Production of chemicals using renewable bioresources and green biomanufacturing processes is highly important for sustainable bioeconomy. Diols are important bulk chemicals widely used in the production of polymers, cosmetics, fuels, food, and pharmaceutical industries due to their versatile functional properties. Currently, most of diols are produced mainly from fossil resources via energy-cost chemical approaches. The development of biosynthetic routes for the production of diols from renewable resources such as biomass and C1 has garnered significant attention due to its potential in reducing the utilization of fossil resources and carbon dioxide emissions. Although biological production of 1,3-propanediol, 1,3-butanediol and 1,4-butanediol has been commercialized, the biosynthesis of most other diols remains challenging due to the absence of efficient natural biosynthetic pathways and low efficiency of the recombinant microbes. Recent development of metabolic engineering and synthetic biology enables the production of non-natural chemicals via artificial metabolic pathways and novel biological parts, significantly expanding the boundary of biomanufacturing. This review comprehensively explores recent advances in the microbial synthesis of diols, emphasizing the development of new pathways and engineering strategies for the biosynthesis of C2 to C5 diols. Especially, we focus on the innovative approaches include constructing non-natural synthetic pathways to achieve the biosynthesis of non-natural diols, or using alternative carbon sources such as lignocellulose through specific metabolic pathways to synthesize diols. Furthermore, this review also discusses the primary challenges and future perspectives in transitioning these biosynthetic processes toward industrial applications. Key challenges involve the accessibility of low-cost and sustainable raw materials, the complexities in scaling up these processes, the development of extraction techniques that cater to specific downstream requirements, and the economic assessment of these processes to ensure profitability and sustainability. These advancements are essential for the economic and environmental viability of producing diols from renewable resources, thereby facilitating the transition to more sustainable industrial practices globally.

Key words: diols, biosynthesis, metabolic engineering, renewable resources, industrial application

中图分类号:

Q812

竺方欢, 岑雪聪, 陈振. 微生物合成二元醇研究进展[J]. 合成生物学, DOI: 10.12211/2096-8280.2024-014.

Fanghuan ZHU, Xuecong CEN, Zhen CHEN. Research progress of diols production by microbes[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2024-014.

图/表 9

图1 乙二醇的生物合成路径（X1P—木糖醛酸-1-磷酸；R1P—核糖醛酸-1-磷酸。图中基因所编码的酶：serA—磷酸甘油酸脱氢酶；serC—磷酸丝氨酸氨基转移酶；serB—磷酸丝氨酸磷酸酶；sdC—丝氨酸脱羧酶；ao—胺氧化酶；agt—丝氨酸-乙醛酸氨基转移酶；mdlC—苯甲酰甲酸脱羧酶；fucO/yqhD—醇脱氢酶；xdh—D-木糖脱氢酶；xylB—木糖激酶；xylC—木糖醛酸酯酶；yjhG/yagF—D-木酮酸脱氢酶；yjhH/yagE—2-酮-3-脱氧-D-戊糖醛缩酶；xylA—D-木糖异构酶；khk-C—D-木糖醛激酶；aldoB—D-木糖醛糖-1-磷酸醛缩酶；dte—D-塔格糖异构酶；fucK—岩藻糖激酶；fucA/rhaD—D-核糖醛糖-1-磷酸醛缩酶）

Fig. 1 Biosynthetic pathways of EG(The enzymes encoded by the genes: serA, phosphoglycerate dehydrogenase; serC, phosphoserine aminotransferase; serB, phosphoserine phosphatase; sdC, L-serine decarboxylase; ao, amine oxidase; agt, serine-glyoxylate aminotransferase; mdlC, benzoylformate decarboxylase; fucO/yqhD, alcohol dehydrogenase; xdh, D-xylose dehydrogenase; xylB, xylulokinase; xylC, xylonolactonase; yjhG/yagF, D-xylonate dehydrogenase; yjhH/yagE, 2-keto-3-deoxy-D-pentose aldolase; xylA, D-xylose isomerase; khk-C, D-xylulose kinase; aldoB, D-xylulose-1-phosphate aldolase; dte, D-tagatose epimerase; fucK, fuculokinase; fucA/rhaD, D-ribulose 1-phosphate aldolase)

表1 生物合成二元醇的典型路径与代谢工程改造策略

Table 1 Typical pathways and metabolic engineering modification strategies for biosynthesis of diols

产物	合成路径	菌株	底物	基因改造策略	产量 (g/L)	得率 (g/g)	生产效率 (g/L/h)	理论转化率（g/g）	文献
乙二醇 (EG)	Dahms路径	Escherichia coli	D-木糖	（1）下调xylB表达（2）过表达yqhD	108.2	0.36	2.25	0.41	[15]
	Dahms路径	Escherichia coli	D-木糖	（1）敲除arcA和aldA；（2）过表达yjhH, xdh, xylC, fucO和yjhG	72.0	0.40	1.38	0.41	[16]
	R1P路径	Escherichia coli	D-木糖	（1）过表达fucK, fucO和fucA （2）敲除ald和xylB	40	0.35	0.58	0.41	[17]
	X1P路径	Escherichia coli	D-木糖	（1）过表达khk-C, aldoB和fucO （2）敲除xylB和ald	20	0.38	0.37	0.41	[19]
	X1P路径	Saccharomyces cerevisiae F251	D-木糖	（1）过表达pfk1和pfk2; （2）敲除xks1	4.05	0.120	0.06	0.41	[18]
	丝氨酸路径	Escherichia coli	葡萄糖	（1）过表达aao, sdc, serABC和fucO （2）敲除aldA	4.1	0.14	-	0.7	[20]
	丝氨酸路径	Corynebacterium glutamicum	葡萄糖	（1）过表达sgt, mdlC, sdc, AO和yqhD （2）插入serACB; （3）敲除pabABC和sdaA	3.5	0.09	-	0.7	[21]
1,2-丙二醇 (1,2-PDO)	丙酮醛途径	K. pneumoniae	甘油	（1）过表达mgsA和yqhD （2）敲除tpiA	9.3	0.2	0.06	0.56	[22]
	丙酮醛途径	Escherichia coli	葡萄糖	（1）过表达mgsA, gldA, fdh1和fucO （2）敲除zwf, tpiA, adhE, gloA和ldhA	5.13	0.48	-	0.56	[23]
	乳酸途径	Escherichia coli	葡萄糖	（1）敲除adhE, dld, lldD, frdA, pflB, mgsA, aldA和arcA	17.3	0.18	0.72	0.56	[24]
1,3-丙二醇 (1,3-PDO)	甘油途径	Escherichia coli	葡萄糖	-	135	3.5	-	0.59	[25]
	甘油途径	Corynebacterium glutamicum	葡萄糖	（1）敲除ald, pyk, adh, poxB, ldhA,ppc和zwf （2）过表达hdpA-gldA, gpd1, gpp2, yqhD, 和pduCEDGH （3）下调表达gapA	110.4	0.42	2.3	0.59	[26]
	甘油途径	Vibrio natriegens	甘油	（1）敲除pta-ackA, arcA, adhE, aldB, ldh, pfl, sthA, glpR, aldA和frdABCD （2）过表达pntAB和phaP	69.5	0.51	2.9	0.67	[27]
	高丝氨酸途径	Escherichia coli	葡萄糖	（1）敲除thrB （2）过表达yqhD, lysC, serC^R42W/R77W, metL和pdc	3.03	-	0.05	0.55	[28]
	丙二酰辅酶A途径	Escherichia coli	葡萄糖	（1）过表达mcrC, pduP, mcrN, yqhD和prpE	7.98	0.15	0.22	0.54	[29]
	β-丙氨酸途径	Escherichia coli	葡萄糖	（1）敲除lysC （2）过表达ppc （3）下调表达gltA	11.21	-	0.10	0.61	[30]
1,3-丁二醇 (1,3-BDO)	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达phaAB和bld	15.75	0.18	0.16	0.53	[31]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达 bld^L273T, yqhD, phaAB和 pntAB （2）敲除ldh, pta, ackA, adhE	13.40	0.30	0.42		[3]
	3-羟基丁酸还原路径	Escherichia coli	葡萄糖	（1）过表达phaAB, yqhD, pntAB, car和sfp （2）敲除ldh, pta, ackA, adhE	0.40	0.02	-		[3]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达 pk, glpX, thl, hbd, tesB和car （2）敲除 zwf, edd, pfkA和pfkB	22.66	0.40	0.32	0.56	[32]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达phaAB, bld和yqhD （2）敲除adhE, poxB, ldhA, pta-ackA, atoB, tesB和yciA	23.10	0.26	0.64		[33]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达phaAB, bld, yjgB和zwf （2）敲除adhE, poxB, ldhA, yciA, pdhR, pgi和gntR	71.10	0.34	1.55		[34]
	DERA-AKR路径	Escherichia coli	葡萄糖	（1）过表达 AKR, DERA和 PDC （2）敲除pta, yjgB, adhE, ldhA, pflB, adhP, yqhD, eutG, ilvB, and poxB;	2.40	0.06	-	0.55	[35]
1,4-丁二醇 (1,4-BDO)	琥珀酰辅酶A路径	Escherichia coli	葡萄糖	-	>125	0.40	>0.35	0.5	[12]
	谷氨酸路径	Escherichia coli	葡萄糖	（1）过表达gadB, gabT, yqhD, car, ppc, gltA^R163L	1.41	0.07	0.03	0.58	[36]
	非磷酸化路径	Escherichia coli	葡萄糖、木糖	（1）敲除yagE, xylA和yjhH （2）过表达Kvid^V461I, xylBCDX和yqhD	12	0.26 （木糖）	0.40	0.41	[37]
1,2-丁二醇 (1,2-BDO)	苏氨酸路径	Escherichia coli	葡萄糖	（1）过表达pyc, thrABC, ilvA, L-ldh, car, yqhD （2）敲除lldd, dld	0.15	-	-	0.48	[38]
2,3- 丁二醇 (2,3-BDO)	丙酮酸路径	Saccharomyces cerevisiae	葡萄糖	（1）过表达BDH1 （2）下调PDC1, PDC6, 和AHD1	178	0.34	2.64	0.5	[39]
2,3- 丁二醇 (2,3-BDO)	丙酮酸路径	Corynebacterium glutamicum	葡萄糖	（1）过表达budABC和acs （2）敲除ldhA, adhE, frdA和pta	144.9	0.43	1.10	0.5	[40]
1,5- 戊二醇 (1,5-PDO)	赖氨酸路径	Escherichia coli	葡萄糖	（1）过表达 lysC^Q298G, asd,ddh, dapA,patA, patD, cadA, gabT, yahk, car, sfp, yqhD （2）敲除gabD, gdhA	9.25	0.16	0.05	0.40	[5]
	赖氨酸路径	Escherichia coli	葡萄糖	（1）过表达 lysC, dapA, davB, davA, gabT, yqhD, car和sfp （2）敲除iclR	0.97	0.05	-	0.38	[36]
	赖氨酸路径	Escherichia coli	葡萄糖	（1）过表达 lysC^Q298G, asd,ddh, dapA, davB, davA, gabT, yqhD, abfT, bld^L273T 和pntAB	0.12	0.006	-	0.3	[41]

表1 生物合成二元醇的典型路径与代谢工程改造策略

Table 1 Typical pathways and metabolic engineering modification strategies for biosynthesis of diols

产物	合成路径	菌株	底物	基因改造策略	产量 (g/L)	得率 (g/g)	生产效率 (g/L/h)	理论转化率（g/g）	文献
乙二醇 (EG)	Dahms路径	Escherichia coli	D-木糖	（1）下调xylB表达（2）过表达yqhD	108.2	0.36	2.25	0.41	[15]
	Dahms路径	Escherichia coli	D-木糖	（1）敲除arcA和aldA；（2）过表达yjhH, xdh, xylC, fucO和yjhG	72.0	0.40	1.38	0.41	[16]
	R1P路径	Escherichia coli	D-木糖	（1）过表达fucK, fucO和fucA （2）敲除ald和xylB	40	0.35	0.58	0.41	[17]
	X1P路径	Escherichia coli	D-木糖	（1）过表达khk-C, aldoB和fucO （2）敲除xylB和ald	20	0.38	0.37	0.41	[19]
	X1P路径	Saccharomyces cerevisiae F251	D-木糖	（1）过表达pfk1和pfk2; （2）敲除xks1	4.05	0.120	0.06	0.41	[18]
	丝氨酸路径	Escherichia coli	葡萄糖	（1）过表达aao, sdc, serABC和fucO （2）敲除aldA	4.1	0.14	-	0.7	[20]
	丝氨酸路径	Corynebacterium glutamicum	葡萄糖	（1）过表达sgt, mdlC, sdc, AO和yqhD （2）插入serACB; （3）敲除pabABC和sdaA	3.5	0.09	-	0.7	[21]
1,2-丙二醇 (1,2-PDO)	丙酮醛途径	K. pneumoniae	甘油	（1）过表达mgsA和yqhD （2）敲除tpiA	9.3	0.2	0.06	0.56	[22]
	丙酮醛途径	Escherichia coli	葡萄糖	（1）过表达mgsA, gldA, fdh1和fucO （2）敲除zwf, tpiA, adhE, gloA和ldhA	5.13	0.48	-	0.56	[23]
	乳酸途径	Escherichia coli	葡萄糖	（1）敲除adhE, dld, lldD, frdA, pflB, mgsA, aldA和arcA	17.3	0.18	0.72	0.56	[24]
1,3-丙二醇 (1,3-PDO)	甘油途径	Escherichia coli	葡萄糖	-	135	3.5	-	0.59	[25]
	甘油途径	Corynebacterium glutamicum	葡萄糖	（1）敲除ald, pyk, adh, poxB, ldhA,ppc和zwf （2）过表达hdpA-gldA, gpd1, gpp2, yqhD, 和pduCEDGH （3）下调表达gapA	110.4	0.42	2.3	0.59	[26]
	甘油途径	Vibrio natriegens	甘油	（1）敲除pta-ackA, arcA, adhE, aldB, ldh, pfl, sthA, glpR, aldA和frdABCD （2）过表达pntAB和phaP	69.5	0.51	2.9	0.67	[27]
	高丝氨酸途径	Escherichia coli	葡萄糖	（1）敲除thrB （2）过表达yqhD, lysC, serC^R42W/R77W, metL和pdc	3.03	-	0.05	0.55	[28]
	丙二酰辅酶A途径	Escherichia coli	葡萄糖	（1）过表达mcrC, pduP, mcrN, yqhD和prpE	7.98	0.15	0.22	0.54	[29]
	β-丙氨酸途径	Escherichia coli	葡萄糖	（1）敲除lysC （2）过表达ppc （3）下调表达gltA	11.21	-	0.10	0.61	[30]
1,3-丁二醇 (1,3-BDO)	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达phaAB和bld	15.75	0.18	0.16	0.53	[31]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达 bld^L273T, yqhD, phaAB和 pntAB （2）敲除ldh, pta, ackA, adhE	13.40	0.30	0.42		[3]
	3-羟基丁酸还原路径	Escherichia coli	葡萄糖	（1）过表达phaAB, yqhD, pntAB, car和sfp （2）敲除ldh, pta, ackA, adhE	0.40	0.02	-		[3]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达 pk, glpX, thl, hbd, tesB和car （2）敲除 zwf, edd, pfkA和pfkB	22.66	0.40	0.32	0.56	[32]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达phaAB, bld和yqhD （2）敲除adhE, poxB, ldhA, pta-ackA, atoB, tesB和yciA	23.10	0.26	0.64		[33]
	3-羟基丁酰辅酶A路径	Escherichia coli	葡萄糖	（1）过表达phaAB, bld, yjgB和zwf （2）敲除adhE, poxB, ldhA, yciA, pdhR, pgi和gntR	71.10	0.34	1.55		[34]
	DERA-AKR路径	Escherichia coli	葡萄糖	（1）过表达 AKR, DERA和 PDC （2）敲除pta, yjgB, adhE, ldhA, pflB, adhP, yqhD, eutG, ilvB, and poxB;	2.40	0.06	-	0.55	[35]
1,4-丁二醇 (1,4-BDO)	琥珀酰辅酶A路径	Escherichia coli	葡萄糖	-	>125	0.40	>0.35	0.5	[12]
	谷氨酸路径	Escherichia coli	葡萄糖	（1）过表达gadB, gabT, yqhD, car, ppc, gltA^R163L	1.41	0.07	0.03	0.58	[36]
	非磷酸化路径	Escherichia coli	葡萄糖、木糖	（1）敲除yagE, xylA和yjhH （2）过表达Kvid^V461I, xylBCDX和yqhD	12	0.26 （木糖）	0.40	0.41	[37]
1,2-丁二醇 (1,2-BDO)	苏氨酸路径	Escherichia coli	葡萄糖	（1）过表达pyc, thrABC, ilvA, L-ldh, car, yqhD （2）敲除lldd, dld	0.15	-	-	0.48	[38]
2,3- 丁二醇 (2,3-BDO)	丙酮酸路径	Saccharomyces cerevisiae	葡萄糖	（1）过表达BDH1 （2）下调PDC1, PDC6, 和AHD1	178	0.34	2.64	0.5	[39]
2,3- 丁二醇 (2,3-BDO)	丙酮酸路径	Corynebacterium glutamicum	葡萄糖	（1）过表达budABC和acs （2）敲除ldhA, adhE, frdA和pta	144.9	0.43	1.10	0.5	[40]
1,5- 戊二醇 (1,5-PDO)	赖氨酸路径	Escherichia coli	葡萄糖	（1）过表达 lysC^Q298G, asd,ddh, dapA,patA, patD, cadA, gabT, yahk, car, sfp, yqhD （2）敲除gabD, gdhA	9.25	0.16	0.05	0.40	[5]
	赖氨酸路径	Escherichia coli	葡萄糖	（1）过表达 lysC, dapA, davB, davA, gabT, yqhD, car和sfp （2）敲除iclR	0.97	0.05	-	0.38	[36]
	赖氨酸路径	Escherichia coli	葡萄糖	（1）过表达 lysC^Q298G, asd,ddh, dapA, davB, davA, gabT, yqhD, abfT, bld^L273T 和pntAB	0.12	0.006	-	0.3	[41]

图2 1，2-丙二醇的生物合成路径（图中基因所编码的酶：gldA/dhaD，甘油脱氢酶；dhaK，PEP依赖型二羟基丙酮激酶；mgsA，甲基乙二醛合酶；yqhD，醇脱氢酶；yahK，醇脱氢酶；fucO，醇脱氢酶；ldhA/lldH，乳酸脱氢酶；pct，丙酸辅酶A转移酶；pduP，醛脱氢酶。）

Fig. 2 Biosynthetic pathways of 1,2-PDO(The enzymes encoded by the genes: gldA/dhaD, glycerol dehydrogenase; dhaK, PEP-dependent dihydroxyacetone kinase; mgsA, methylglyoxal synthase; yqhD, alcohol dehydrogenase; yahK, alcohol dehydrogenase; fucO, alcohol dehydrogenase; ldhA/lldH, lactate dehydrogenase; pct, propionate CoA-transferase; pduP, aldehyde dehydrogenase.)

图3 1，3-丙二醇的生物合成路径（图中基因所编码的酶：gpd，甘油-3-磷酸脱氢酶；gpp2，甘油-3-磷酸磷酸酶；dhaBCE，维生素B12依赖的甘油脱水酶；dhaT/yqhD，醇脱氢酶；acc，乙酰辅酶A羧化酶；mcr，丙二酰辅酶A还原酶；prpE，3-羟基丙酰辅酶A合成酶；pduP，醛脱氢酶；car，羧酸还原酶；mdh，甲醇脱氢酶；adh，醇脱氢酶；DERA，脱氧核糖-5-磷酸醛缩酶；aspC，天冬氨酸转氨酶；panD，天冬氨酸脱羧酶；bauA，β-丙氨酸-丙酮酸氨基转移酶；ydfG，3-羟基酸脱氢酶；M_1456，3-羟基丙酰辅酶A合酶；lysC，苹果酸激酶；asd，苹果酸半醛脱氢酶；ssr，苹果酸半醛还原酶；lldD，乳酸脱氢酶；kdc，酮酸脱羧酶；pdc，丙酮酸脱羧酶；gdhA，谷氨酸脱氢酶；serC，磷酸丝氨酸氨基转移酶。）

Fig. 3 Biosynthetic pathways of 1,3-PDO(The enzymes encoded by the genes: gpd, glycerol-3-phosphate dehydrogenase; gpp2, glycerol-3-phosphate phosphatase; dhaBCE, vitamin B12-dependent glycerol dehydratase; dhaT/yqhD, alcohol dehydrogenase; acc, acetyl-CoA carboxylase; mcr, malonyl-CoA reductase; prpE, 3-hydroxypropionyl-CoA synthetase; pduP, aldehyde dehydrogenase; car, carboxylic acid reductase; mdh, methanol dehydrogenase; adh, alcohol dehydrogenase; DERA, deoxyribose-5-phosphate aldolase; aspC, aspartate transaminase; panD, aspartate decarboxylase; bauA, β-alanine-pyruvate aminotransferase; ydfG, 3-hydroxy acid dehydrogenase; M_1456, 3-hydroxypropionyl-Coenzyme A synthetase; lysC, malate kinase; asd, malate semialdehyde dehydrogenase; ssr, malate semialdehyde reductase; lldD, lactate dehydrogenase; kdc, ketoacid decarboxylase; pdc, pyruvate decarboxylase; gdhA, glutamate dehydrogenase; serC, phosphoserine aminotransferase.)

图4 1，3-丁二醇的生物合成路径（图中基因所编码的酶：adhE，醇脱氢酶；DERA，脱氧核糖-5-磷酸醛缩酶；yqhD，醇脱氢酶；phaA，乙酰辅酶A乙酰转移酶；phaB，乙酰乙酰辅酶A还原酶；bld，3-羟基丁酰辅酶A脱氢酶；car，羧酸还原酶。）

Fig. 4 Biosynthetic pathways of 1,3-BDO(The enzymes encoded by the genes: adhE, alcohol dehydrogenase; DERA, deoxyribose-5-phosphate aldolase; yqhD, alcohol dehydrogenase; phaA, acetyl-CoA acetyltransferase; phaB, acetoacetyl-CoA reductase; bld, 3-hydroxybutyryl-CoA dehydrogenase; car, carboxylic acid reductase.)

图5 1，4-丁二醇的生物合成路径（图中基因所编码的酶：gdhA，谷氨酸脱氢酶；gadB，谷氨酸脱羧酶；gabT，转氨酶；sucD，琥珀酸半醛脱氢酶；yqhD/4hbd/adh，醇脱氢酶；cat2，4-羟基丁酸辅酶A转移酶；ald，醛脱氢酶；car，羧酸还原酶；xylBC，D-木糖脱氢酶；xylD/yjhG/yagF，D-木酮酸脱水酶；xylX/hvo/kdxD，2-酮-3-脱氧-D-木酮酸脱水酶；sadh，醇脱氢酶；kivD/mdlC，脱羧酶。）

Fig. 5 Biosynthetic pathways of 1,4-BDO(The enzymes encoded by the genes: gdhA, glutamate dehydrogenase; gadB, glutamate decarboxylase; gabT, aminotransferase; sucD, succinate semialdehyde dehydrogenase; yqhD/4hbd/adh, alcohol dehydrogenase; cat2, 4-hydroxybutyrate-CoA transferase; ald, aldehyde dehydrogenase; car, carboxylic acid reductase; xylBC, D-xylose dehydrogenase; xylD/yjhG/yagF, D-xylonate dehydratase; xylX/hvo/kdxD, 2-keto-3-deoxy-D-xylonate dehydratase; sadh, alcohol dehydrogenase; kivD/mdlC, decarboxylase.)

图6 2，3-丁二醇的生物合成路径（图中基因所编码的酶：budB，乙酰乳酸合酶；budA，乙酰乳酸脱羧酶；budC，2，3-丁二醇脱氢酶。）

Fig. 6 Biosynthetic pathways of 2,3-BDO(The enzymes encoded by the genes: budB, acetolactate synthase; budA, acetolactate decarboxylase; budC, 2,3-butanediol dehydrogenase.)

图7 1，2-丁二醇的生物合成路径（图中基因所编码的酶：pyc，丙酮酸羧化酶；aspC，天冬氨酸转氨酶；thrA，高丝氨酸脱氢酶；asd，天冬氨酸半醛脱氢酶；thrB，高丝氨酸激酶；thrC，苏氨酸合酶；ilvA，L-苏氨酸脱水酶；L-ldh，L-乳酸脱氢酶；car；羧酸还原酶；yqhD，醇脱氢酶。）

Fig. 7 Biosynthetic pathway of 1,2-BDO(The enzymes encoded by the genes: pyc, pyruvate carboxylase; aspC, aspartate transaminase; thrA, homoserine dehydrogenase; asd, aspartate semialdehyde dehydrogenase; thrB, homoserine kinase; thrC, threonine synthase; ilvA, L-threonine dehydratase; L-ldh, L-lactate dehydrogenase; car, carboxylic acid reductase; yqhD, alcohol dehydrogenase.)

图8 1，5-戊二醇的生物合成路径（图中基因所编码的酶：davB，赖氨酸单加氧酶；davA，5-氨基己酰胺酶；gabT，4-氨基丁酸转氨酶；yqhD/yahK，醇脱氢酶；car，羧酸还原酶；abfT，5-羟基戊酸辅酶A转移酶；bld，醛脱氢酶；cadA，赖氨酸脱羧酶；patA，丁二胺转氨酶；patD，醇脱氢酶。）

Fig. 8 Biosynthetic pathways of 1,5-PDO(The enzymes encoded by the genes: davB, lysine monooxygenase; davA, 5-aminovaleramidase; gabT, 4-aminobutyrate aminotransferase; yqhD/yahK, alcohol dehydrogenase; car, carboxylic acid reductase; abfT, 5-hydroxyvalerate-CoA transferase; bld, aldehyde dehydrogenase; cadA, lysine decarboxylase; patA, putrescine aminotransferase; patD, alcohol dehydrogenase.)

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