Metabolic rewiring of microbial cell factories for improved production of succinic acid

Das, Satwika; Sharma, Kriti; Sharmmah, Debosmita; Sharma, Shagun; Sevda, Surajbhan; Prabhu, Ashish A.

doi:10.1186/s44316-024-00012-z

Biotechnology for Sustainable Materials

Table 1 Metabolic engineering of heterologous host for the production of SA

From: Metabolic rewiring of microbial cell factories for improved production of succinic acid

Engineering Strategy					Titer (g/L)	Productivity (g/L/h)	Yield (g/g)		By-product	Reference
*Escherichia coli*
Overexpression of ppc gene expressing PEP carboxykinase	Glucose	Batch, Anaerobic			10.7	0.594	0.29		Ethanol, Lactate, Acetate, Formate	[32]
Overexpression of heterologous pyc	Glucose	Batch, Anaerobic			1.77	0.177	0.177		Lactate, Formate	[85]
Δldh and Δpfl gene, Overexpression of sfcA gene	Glucose	Batch, Anaerobic			12.8	0.29	0.64		Acetate Formate	[37]
Δldh and Δpfl gene, Mutation in ptsG gene	Glucose	Fed-Batch, Dual Phase Aeration			-	0.87	0.65		Acetate, Ethanol	[40]
	Glucose	Fed-Batch, Anaerobic			-	-	0.60		Acetate, Ethanol	[39]
	Glucose	Fed-Batch, Anaerobic			-	-	0.88		Acetate, Ethanol	[86]
Overexpression of pyc	Glucose	Fed-Batch, Dual Phase Aeration			99.2	1.3	1.1		Pyruvate, Formate	[40]
Mutation in ptsG21 gene, followed by Δpfl and ΔldhA gene,	Glucose	Batch, Dual Phase Aeration			-	-	0.88		Acetate	[41]
	Fructose	Batch, Dual Phase Aeration			-	-	0.44		Acetate, Formate, Malate	[41]
	Glucose and Fructose (1:1)	Batch, Dual Phase Aeration			-	-	0.71		Acetate. Formate	[41]
ΔadhE, ΔldhA genes; and overexpression of heterologous pyc from Lactococcus lactis	Glucose	Batch, Anaerobic			15.6	0.65	0.83		Formate. Acetate	[42]
ΔptsG system	Glucose	Batch, Anaerobic			-	-	0.91		Formate. Acetate	[42]
ΔadhE, ΔldhA, and Δack-pta, ΔiclR gene inactivation; overexpression of heterologous pyc from Lactococcus lactis	Glucose	Fed-batch, anaerobic			40	0.42	1.06		Formate. Acetate	[43]
ΔadhE, ΔldhA, and Δack-pta; overexpression of heterologous pyc from Lactococcus lactis	Glucose	Batch, Anaerobic			15.9	0.64	1.07		Formate	[87]
ΔiclR, ΔsdhAB, Δicd, Δ (ackA-pta), ΔpoxB	Glucose	Batch, Aerobic			4.61	0.06	0.43		Pyruvate, Acetate	[44]
Overexpression of sorghum pepc	Glucose	Batch, Aerobic			9	0.14	0.72		Pyruvate, Acetate	[44]
ΔldhA, ΔadhE, ΔackA, ΔfocA-pflB	Glucose	Fed-batch, Anaerobic			86.6	0.9	0.92		Malate, acetate	[46]
ΔldhA, ΔadhE, ΔackA, ΔfocA-pflB, ΔmgsA, ΔpoxB	Glucose	Fed-batch, Anaerobic			78.8	0.82	0.79		Acetate, Pyruvate, Malate	[46]
Δpta-ackA in KJ122(ΔldhA, ΔadhE, ΔfocA-pflB, ΔmgsA, ΔpoxB, ΔtdcDE, ΔcitF, ΔaspC, ΔsfcA)	Glucose	Fed-batch, Anaerobic			71.6	0.75	1		Acetate, Pyruvate, Malate	[47]
*Corynebacterium glutamicum*
ΔldhA	Glucose	Micro-aerobic, fed-batch with membrane for cell recycling			23	3.83	0.19		Lactate	[51]
ΔldhA, Over-expressed pyc	Glucose	Two stages – aerobic growth / Anaerobic fed-batch			146	3.17	0.92		Acetate	[52]
ΔldhA Δpta Δpqo ΔcatP_sod-ppcP_sod-pyc Expression of xylA, xylB, araE over- expression of tkt and tal	Corn stalk	Two stage, aerobic culture of biomass and anaerobic batch fermentation, minimal medium			98.6	4.29	0.87		-	[88]
araBAD from Escherichia coli was inserted	Arabinose	Aerobic			74.4	0.36	0.58		Acetate Pyruvate	[53]
araBAD from Escherichia coli was inserted	Glucose and arabinose				110.2	0.28	0.56 (mol substrate)⁻¹		Acetate Pyruvate	[53]
ΔldhA gene	Arabinose	Two-stage fermentation system in screw-cap tube			1.74	0.87	0.89		-	[54]
	Glucose and arabinose				1.31	0.22	0.63		-
	Glucose and Sucrose				3.31	0.41	1.48		-
	Sucrose and Arabinose				2.85	0.36	1.28		-
	Glucose, Sucrose and Arabinose				2.84	0.36	1.17		-
Δcat, Δpqo, Δpta-ackA, ΔldhA, over-expression of native pyc and Mycobacterium vaccae fdh	Glucose	Two stages – aerobic culture/ anaerobic fed- batch production			82	1.60	0.36		Acetate	[55]
Δcat Δpqo Δpta- ackA ΔldhA over-expression of native pyc and Mycobacterium vaccae fdh	Glucose	Two stages – aerobic culture/ anaerobic fed- batch production			134	2.48	1.67		-	[89]
Expression of E. coli glpFKD operon	Glycerol	Fed-batch, aerobic culture			9.3	0.423	0.42		-	[56]
ΔldhA derivative with additional in-frame deletion of NCgl2130	Glucose	Fermentation culture under microaerobic and anaerobic conditions,			8.1	3.24	0.56		-	[58]
Corynebacterium glutamicum AJ13869DsdhA/pVK9::PmsrA-CgynfM AJ110655	Glucose	Aerobic condition			110	15	0.33		-	[59]
Corynebacterium glutamicum FK948/pVK9::PmsrA-CgynfM (deleted sucE1 gene)	Glucose	Anaerobic condition			270	15.3	-		-	[59]
Δldh, Δpta-ackA, ΔactA, ΔpoxB, pycP458, Δpck_Ptuf::Ms.pckG, Ptuf::ppc, ΔptsG Over-expression of NCgl0275	Glucose	One stage – aerobic culture/anaerobic fed- batch production			152.2	1.11	1.10		-	[90]
ΔaceE Δpqo ΔldhA ΔC-T ilvN ΔalaT ΔavtA ΔPDHC, ΔPQO	Glucose	One stage fed-batch fermentation			38.9	0.66	0.67		Pyruvate	[91]
BL-1 harboring pBbEB1c-torA-SbAmyA	Micro-algal starch	Minimal medium Sequential aerobic fermentations of CO₂-grown micro-algae and engineered C. glutamicum			0.5	0.021	0.28		-	[92]
ΔldhA chromosomal integration into the pta-ackA locus of xylA and xylB gene from E. coli	Corn cob Hydrolysate (Xylose + Glucose), bi-carbonate	Two-stage, aerobic culture of biomass and anaerobic batch fermentation, minimal medium			40.8	0.85	0.69 (mol/mol)		Acetate, Pyruvate	[93]
Expression of acetyl-CoA synthetase Over-expression of gltA gene (citrate synthase)	Glucose	Minimal medium Aerobic growth Fed-batch culture			241 (mM)	3.55 (mM h⁻¹)	0.62 (mol/mol)		-	[57]
*Saccharomyces cerevisiae*
Δsdh2, Δsdh1, Δidh1, Δidp1	Glucose		Batch, Aerobic		3.62	0.022	0.072	Ethanol, Glycerol, Acetate		[65]
Δsdh3, Δser3, Δser33	Glucose		Batch, Aerobic		0.60	-	0.03	-		[69]
Evolved 8D with icl1	Glucose		Batch, Aerobic		0.90	-	0.05	-		[69]
*Yarrowia lipolytica*
Δsdh5	Crude glycerol			Aerobic Fed-batch	160	0.4	0.4	Acetic acid		[94]
sΔsdh5, overexpression of ScPCK, YlSCS2	Glycerol			Aerobic Fed-batch	110.7	-	0.53	Mannitol		[84]
Δsdh5, overexpression of XR, XDH, XK	Xylose			Aerobic Fed-Batch	22.3	-	0.15	Acetic acid		[95]

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