Research progress of diols production by microbes

doi:10.12211/2096-8280.2024-014

Abstract

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

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

CLC Number:

Q812

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

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.

Figures/Tables 9

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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]

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]

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