Table 3.

Genes involved in metabolism of furfural in microbial biocatalysts

Organism	Conc	Target gene	Function	Culture conditions	Parameter tested∏	Reference
E. coli	1.5 g/L	thyA↑, lpcA↑, groESL↑	thyA – thymidylate synthase; lpcA – D-sedoheptulose 7-phosphate isomerase; groESL – chaperonin complex induced under heat shock	MOPS minimum medium with glucose	Biomass increase#: lpcA ~ 400% groESL ~ 100%	[34]
	10 mM	thyA↑	-As before-	AM1 minimum medium with xylose	Ethanol titer: ND*; ~ 30 g/L	[52]
	1.5 g/L	thyA↑, ahpC↑, yhjH↑	ahpC – component of alkyl hydroperoxide reductase; yhjH – c-di-GMP phosphodiesterase, regulation in switch from flagellar motility to sessile	MOPS minimum medium with glucose	Biomass increase#: yhjH ~ 300%, ahpC ~ 80%	[33]
	1.25 g/L	mdtJI↑, sugE↑	mdtJI – components of multidrug efflux transporter; sugE – proton coupled guanidium transporter	AM1 minimum medium with xylose	Biomass: ND*; mdtJI, sugE OD600 ~ 1.5 Ethanol productivity: 0.19 g/L/h*; mdtJI 0.42 g/L/h	[65]
	10 mM	puuP↑, potE↑	Proton dependent putrescine transporters	AM1 minimum medium with xylose	Ethanol titer: ND*; puuP, potE ~ 42 g/L	[66]
	1 g/L+	∆pgi	Interconversion of G6P to F6P in glycolysis	AM1 minimum medium with glucose-xylose mixture	Ethanol titer: ~ 2 g/L*; pgi ~ 20 g/L	[68]
	1 g/L	∆yqhD, ∆dkgA	yqhD – aldehyde reductase; dkgA – methylglyoxal and beta-keto ester reductase	Acid treated sugarcane bagasse	Double mutant with 3 and tenfold higher biomass and ethanol, respectively, as compared to the control	[69]
	1 g/L	pntAB↑	Membrane bound proton translocating, pyridine nucleotide tranhydrogenase, reduces NADP +	AM1 medium with xylose	Biomass: < 0.1 g/L*; pntAB ~ 0.5 g/L	[71]
	15 mM	fucO↑	Reduces L-lactaldehyde to L-1,2-propanediol	Acid treated sugarcane bagasse	Ethanol titer: < 5 g/L*; fucO ~ 42 g/L	[105]
	1 g/L	yghA↑	Reductase activity toward butyraldehyde and decanal	AM1 with xylose	Ethanol productivity: ND*; yghA 0.72 g/L/h	[73]
	2 g/L	mutant irrE↑	Global regulator in radioresistance in Deinococcus radiodurans	Acid treated corn stover hydrolysate	Biomass: ND*; mutant irrE OD600 ~ 2.5	[74]
	10 mM	ucpA↑	Predicted acetoin dehydrogenase	AM1 medium with xylose	Ethanol titer: 0.55 g/L*; ucpA 40.3 g/L	[118]
	0.5 g/L	cysC, cysH, cysM, cysN, cysQ, metA, metB, metC, sbp, tauA, tauB, tauC, tauD^	cysH, cysH, cysM, cysN, cysQ – involved in sulfur metabolism; metA, metB, metC – de novo methionine biosynthesis; sbp – high affinity uptake of sulfate and thiosulfate; tauA, tauB, tauC, tauD – taurine uptake system	AM1 medium with xylose	Biomass: ND*; Cysteine supplementation ~ 1.5 g/L	[71]
S. cerevisiae	25 mM	∆ZWF1, ∆GND1, ∆RPE1, ∆TKL1	ZWF1 – glucose-6-phosphate dehydrogenase; GND1 – 6-phosphogluconate dehydrogenase; RPE1 – D-ribulose-5-phosphate 3-epimerase; TKL1 – transketolase	SD medium with glucose	WT parent ~ 20% growth inhibition*; Deletion of each gene resulted in at least 80% growth inhibition	[47]
	30 mM	YAP1↑, GSH1↑, GLR1↑	YAP1 – basic leucine zipper (bZIP) transcription factor; GSH1 – gamma glutamylcysteine synthetase, glutathione biosynthesis; GLR1 – cytosolic and mitochondrial glutathione oxidoreductase	YPD medium with glucose	Biomass: OD600 < 0.1*; YAP1 OD600 ~ 0.8; GSH1 ~ 0.7; GLR1 ~ 0.7	[54]
	2 g/L	SPE3↑	Spermidine synthase	Acid treated corn stover hydrolysate	Ethanol productivity: 0.13 g/L/h*; SPE3 – 0.24 g/L/h	[85]
	4 g/L	GLR1↑, OYE2↑, ZWF1↑, IDP1↑	OYE2 – FMN containing oxidoreductase; IDP1 – mitochondrial isocitrate dehydrogenase	YPD medium with glucose	Biomass: OD600 ~ 0.8*; Overexpression of each gene separately ~ 1.0 Ethanol titer: ~ 35 g/L*; IDP1, GLR1 ~ 45 g/L; OYE1, ZWF1 ~ 40 g/L	[119]
	15 mM	MSN2↑	Stress-responsive transcriptional activator	SC medium with glucose	Biomass: OD600 ~ 3.5*; MSN2 ~ 6.0	[120]
Caldicellulosiruptor bescii	15 mM	bdhA↑	Butanol dehydrogenase	LOD medium with maltose/cellobiose as carbon source	Biomass: 0.4 g/L*; bdhA 0.5 g/L	[95]
Clostridium thermocellum	10 mM	bdhA↑, speE↑	speE – spermidine synthase	CTFUD medium with cellobiose	Biomass: OD600 ~ 0.3*; co-expression of bdhA speE ~ 0.9 Ethanol titer: 6 mM; co-expression of bdhA speE 7 mM	[90]
Candida tropicalis	1 g/L	ADH1↑	Alcohol dehydrogenase	M9 medium with glucose	~ 60% furfural removed from medium by control*; 100% furfural removed from medium by overexpression of ADH1	[93]
Zymomonas mobilis	0.69 g/L	udhA (co-expressed with ZMO1771)	Soluble pyridine nucleotide transhydrogenase, reduces NAD+	Acid treated corn stover hydrolysate	Biomass: OD600 ~ 0.75*; co-expression of udhA ZMO1771 ~ 1.20 Ethanol titer: ~ 21 g/L*; co-expression of udhA ZMO1771 ~ 30 g/L	[91]
Pseudomonas putida	2 g/L (and 1 g/L 5-HMF)	psJN↑	Oxidoreductase, converts aldehydes into corresponding acid	Acid treated corn stover hydrolysate	Biomass: OD600 ~ 0.5*; psJN ~ 2.5	[103]
	20 mM	PP_RS19785↑, PP_RS18130↑	Putative ABC-type transporters with efflux activity	Hydrolysate conditions	Biomass: OD600 ~ 9-fold (PP_RS19785) and 3.6-fold (PP_RS18130) higher as compared to the control	[104]

^∏Genes were expressed separately and case of co-expression is mentioned in the table. ND - signifies Not Detected. ⁺1 g/L 5-HMF was also present in the medium.

^*Represents value of the control strain

^#Percent increase in biomass as compared to the control strain

↑Indicates overexpression and ∆ indicates deletion

^Microarray results indicated downregulation of genes involved in sulfur assimilation in presence of furfural and the study tested supplementation with cysteine as a sulfur source in presence of furfural