Development of bio-based fine chemical production through synthetic bioengineering

Hara, Kiyotaka Y; Araki, Michihiro; Okai, Naoko; Wakai, Satoshi; Hasunuma, Tomohisa; Kondo, Akihiko

doi:10.1186/s12934-014-0173-5

Microbial Cell Factories

Table 3 Strategies of synthetic bioengineering for the microbial production of isoprenoids

From: Development of bio-based fine chemical production through synthetic bioengineering

Compounds	Host strains	Genetic engineering ^a	Strategy for flux control	Titer	Reference
Isoprene	E. coli	He: B. subtilis dxs, dxr and P. alba IspS	-Improvement of MEP pathway flux	314 mg/L	Zhao et al., 2011 [30]
	E. coli	He: P. alba IspS	-Integration of heterologous MVA pathway	532 mg/L	Yang et al., 2012 [34]
	E. coli	Oe: MVA pathway genes	-Integration of heterologous MVA pathway	532 mg/L	Yang et al., 2012 [34]
*Monoterpene*
Carene	E. coli	He: H. pluvialis IPI isomerase and P. abies 3- carene cyclase genes	-Improvement of flux toward GPP	3 μg/L/OD₆₀₀	Reiling et al., 2004 [41]
Carene	E. coli	Oe: dxs, IspA variant	-Improvement of flux toward GPP	3 μg/L/OD₆₀₀	Reiling et al., 2004 [41]
Geraniol	S. cerevisiae	He: O. basiilcum geraniol synthase gene	-Repression of FPP synthesis	5 mg/L	Fischer et al., 2011 [40]
Geraniol	S. cerevisiae	Mu: ERG20	-Repression of FPP synthesis	5 mg/L	Fischer et al., 2011 [40]
Linalool	S. cerevisiae	He: C. breweri LIS	-Improvement of MVA pathway flux	132.66 μg/L	Rico et al., 2010 [39]
Linalool	S. cerevisiae	Oe: tHMG1	-Improvement of MVA pathway flux	132.66 μg/L	Rico et al., 2010 [39]
*Sesquiterpene*
Artemisinic acid (Amorpha-4,11-diene)	E. coli	He: S. cerevisiae HMGS, tHMG1, ERG12, ERG8, MVD1, H. pluvialis ispA and A. annua ADS	-Integration of heterologous MVA pathway	111.2 mg/L	Martin et al., 2003 [53]
			-Overexpression of FPP synthase gene
		Oe: atoB and idi	-Overexpression of FPP synthase gene
	S. cerevisiae	He: A. annua ADS and CYP71AV1	-Overexpression of tHMGR and FPP synthase genes	153 mg/L	Ro et al., 2006 [54]
		Oe: tHMG1, ERG20 and Upc2-1	-Overexpression of tHMGR and FPP synthase genes
		Oe: tHMG1, ERG20 and Upc2-1	-Up regulation of global transcription activity
		Dr: ERG9	-Up regulation of global transcription activity
		Dr: ERG9	-Repression of squalene synthesis
		He: A. annua ADS, CYP71AV1, CPR1, CYB5, ALDH1 and ADH1	-Integration of heterologous MVA pathway	25 g/L	Paddon et al., 2013 [55]
			-Overexpression of tHMGR and FPP synthase genes
			-Repression of
			squalene synthesis
		Oe: MVA pathway genes, tHMGR, and ERG20
		Dr: ERG9
Levopi-maradiene	E. coli	He: G. biloba GGPPS and LPS	-Improvement of flux toward IPP/DMAPP	700 mg/L	Leonard et al., 2010 [49]
Levopi-maradiene	E. coli	Oe: dxs, idi, ispD and ispF	-Combinatorial mutation in GGPP synthase and LPS	700 mg/L	Leonard et al., 2010 [49]
Patchoulol	S. cerevisiae	Oe: S. cerevisiae FPPS/P. cablin PTS (chimera)	-Avoidance of intermediate loss	40.9 mg/L	Albertsen et al., 2011 [43]
		Oe: S. cerevisiae FPPS/P. cablin PTS (chimera)	-Repression of squalene synthesis
		Dr: ERG9	-Repression of squalene synthesis
α-Santalene	S. cerevisiae	He: C. lansium santalene synthase	-Overexpression of tHMGR and FPP synthase	92 mg/L	Scalcinati et al., 2012 [42]
		Oe: tHMG1, FPPS, GDH2 and Upc2-1	-Overexpression of tHMGR and FPP synthase
		Oe: tHMG1, FPPS, GDH2 and Upc2-1	-Increment of cofactor supply
		Dr: ERG9	-Increment of cofactor supply
		De: GDH1, LPP1, DPP1	-Up regulation of global transcription activity
			-Repression of squalene synthesis
			-Minimization of flux toward farnosol
		He: C. lansium santalene synthase	-Improvement of flux toward acetoacetyl-CoA from ethanol	8.3 mg/L	Chen et al., 2013 [44]
		He: C. lansium santalene synthase	-Avoidance of acetyl-CoA consumption
		Oe: Adh2, Ald6, ACS variant, Erg10 and tHMG1
		De: CIT2 and MLS1
Valencene	S. cerevisiae	He: A. thaliana FPP synthase and C. sinensis TPS1 genes in mitochondria	-Overexpression of tHMGR	1.5 mg/L	Farhi et al., 2011 [44]
			-Mitochondrial expression of FPP synthase and valencene synthase genes
		Oe: tHMG1
*Diterpene*
Casbene	E. coli	Oe: dxs, IspA variant	-Improvement of flux toward GGPP	0.3 mg/L	Reiling et al., 2004 [41]
Casbene	E. coli	He: H. pluvialis IPI isomerase and R. communis casbene cyclase genes	-Improvement of flux toward GGPP	0.3 mg/L	Reiling et al., 2004 [41]
Miltiradiene	S. cerevisiae	He: S. acidocaldarium GGPPS and S. miltiorrhizha CPS and KSL	-Overexpression of tHMGR, FPP synthase and GGPP synthase genes	8.8 mg/L	Dai et al., 2012 [47]
Miltiradiene	S. cerevisiae	Oe: tHMG1, ERG20, BTS1 and Upc2-1	-Up regulation of global transcription activity	8.8 mg/L	Dai et al., 2012 [47]
Taxadiene	E. coli	He: S. acidocaldariums GGPP synthase and T. chinensis taxadiene synthase genes	-Improvement of MEP pathway flux	1 g/L	Ajikumar et al., 2010 [24]
			-Overexpression of GGPP synthase
		Oe: dxs, ispC, ispF, idi, tHMG1 and Upc2-1	-Overexpression of GGPP synthase
	S. cerevisiae	He: S. acidocaldariums GGPP synthase and T. chinensis taxadiene synthase genes	-Overexpression of tHMGR	8.7 mg/L	Engels et al., 2008 [31]
			-Up regulation of global transcription activity
		Oe: tHMG1 and Upc2-1	-Up regulation of global transcription activity
*Triterpene*
β-Amyrin	S. cerevisiae	Oe: tHMG1	-Overexpression of tHMGR	6 mg/L	Kirby et al., 2008 [52]
		He: A. annua β-amyrin synthase gene	-Overexpression of tHMGR
		He: A. annua β-amyrin synthase gene	-Repression of lanosterol synthesis
		Dr: ERG7	-Repression of lanosterol synthesis

^aTypes of genetic engineering: He, Heterologous expression; Oe, Overexpression of self-cloning gene(s); Dr, down regulation; De, Deletion; Mu, Mutation.

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ISSN: 1475-2859

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