Table 1.
Example of products and strains of S. cerevisiae
| Categories | Products | Specific applications | Strains | References |
|---|---|---|---|---|
| Biofuels | Ethanol | Redox balance problem by inhibiting glycerol formation in anaerobic culture was solved by combining gene deletion (GPD1 and GPD2) and integration (mhpF from E. coli) with acetic acid supplementation, which was presented at substantial quantities in lignocellulosic hydrolysates of agricultural residues | CEN.PK102-3A (MATa ura3 leu2) | [17] |
| Biobutanol | Overexpression of genes in valine metabolism, ILV2, ILV3, ILV5, and BAT2 showed an increased production of isobutanol in S. cerevisiae, which strain was decided as a host because of relative tolerance to alcohols, and robustness in industrial fermentation | CEN.PK 2-1C (MATα leu2-3, 112 his3-Δ1 ura3-52 trp1-289 MAL2-8(Con) MAL3 SUC3) | [18] | |
| Biodiesels | Glycerol utilization for production of fatty acid ethyl esters (FAEEs) was done by amplification of ethanol production pathway, which is used for the transesterification in FAEEs synthesis, with overexpression of an unspecific acyltransferase from Acinetobacter baylyi | YPH499 (MATa ura3-52 lys2-801_amber ade2-101_ochre trp1-D63 his3-D200 leu2-D1) | [19] | |
| Bisabolene (D2 diesel fuel, bisabolane) | Bisabolene, the immediate precursor to bisabolane, was produced by (1) using the strategy for increasing pool of farnesyl diphosphate (FPP) in artemisinic acid production [20] and (2) screening and codon-optimizing bisabolene synthases (sesquiterpene synthases). The final titers were over 900 mg/l in shake flasks | BY4742 (MATα his3D1 leu2D0 lys2D0 ura3D0) | [21] | |
| Bulk chemicals | 1,2-propanediol | The combination effects of different copy number (from 0 to 3) of two E. coli genes (mgs and gldA) ware studied. Although the three copy numbers of two genes showed the highest level of 1,2-propanediol, specific activity of Mgs and inhibitory relationship by GldA was considered more importantly for the production of 1,2-propanediol |
NOY386αA (MATα ura3-52 lys2-801 trp1-Δ63 his3-Δ200 leu2-Δ1) BWG1-7a (MATa ade1-100 his4-519 leu2-3,112 ura3-52 GAL +) |
[22] |
| d-ribose and ribitol | The flux from glucose to pentose phosphate pathway was amplified by inactivation of both phosphoglucose isomerase and transketolase with overexpression of sugar phosphate phosphatase (DOG1). Fructose was supplied and redox balance was controlled by overexpression of NAD+-specific glutamate dehydrogenase (GDH2) of S. cerevisiae or NADPH-utilizing glyceraldehyde-3-phosphate dehydrogenase (gapB) of Bacillus subtilis | CEN.PK2-1D (VW-1B; MATα, leu2-3/112 ura3-52 trp1-289 his3Δ1 MAL2-8c SUC2) | [23] | |
| l-lactic acid | Improved production of l-lactic acid was achieved by overexpression of LDH gene coding l-lactic acid dehydrogenase from bovine and knocked out a PDC1 gene coding pyruvate decarboxylase to redirect the fluxes to l-lactic acid; and overexpression of an NADH oxidase (nox) from Streptococcus pneumoniae into the cytoplasm to reduce the ratio of NADH/NAD+ | CEN. PK2-1C (MATa ura3-52 trp1-289 leu2-3,112 his3Ä1 MAL2-8C SUC2) | [24] | |
| Polyhydroxy-alkanoates | The synthesis of diverse size of PHA polymer (C4 to C14) was investigated by cytosolic expression of mcl-PHA synthase from Pseudomonas oleovorans or peroxisomal expression of scl-PHA synthase from Ralstonia eutropha | BY4743 (MATa/α his3Δ1/his3Δ1 leu2Δ0/leu2Δ0 ura3Δ0/ura3Δ0) | [25] | |
| Pyruvic acid | Pyruvate decarboxylase-negative [Pdc(−)] strains were evolved in glucose-limited chemostat cultivation by progressively lowering the acetate content in the feed to obtain an acetate-independent Pdc (−) mutant. Maximum yield was 0.54 g of pyruvate/g glucose | CEN.PK113-7D (MATa MAL2-8C, SUC2) | [26] | |
| Succinic acid | The deletion of the genes SDH1, SDH2, IDH1, and IDP1 made higher flux to succinic acid production. Maximum yield was 0.11 mol of succinic acid/mol of glucose | AH22ura3 (MATa ura3Δ leu2-3 leu2-112 his4-519 can1) | [27] | |
| Fine chemicals | β-amyrin | The differences of phenotype and genotype in two yeast strains, CEN.PK113-7D and S288C, were compared. CEN.PK113-7D had more contents of ergosterol and fatty acids with non-silent SNPs in relative metabolism, ERG8, ERG9, and HFA1. Amplification of those genes exhibited a fivefold increase of β-amyrin | CEN.PK113-7D (MATa MAL2-8C SUC2) | [28] |
| β-carotene | Genomic integration and overexpression of carotenogenic genes from X. dendrorhous (crtYB, crtE, and crtI) and S. cerevisiae (BTS1 and truncated HMG1) with change of copy number achieved high levels of β-carotene, up to 5.9 mg/g dry cell weight | CEN.PK113-7D (MATa MAL2-8C SUC2) | [29] | |
| Amorpha-4, 11- diene | Amplification of mevalonate pathway in CEN.PK2 was engineered and compared to previously constructed strain S288C [20]. Artemisinic acid production was doubled, while amorpha-4, 11-diene was tenfold higher, over 40 g/l |
CEN.PK2-1C (MATa ura3-52 trp1-289 leu2-3,112 his3Ä1 MAL2-8C SUC2) CEN.PK2-1D (MATα ura3-52 trp1-289 leu2-3,112 his3Ä1 MAL2-8C SUC2) |
[30] | |
| Valencene and amorphadiene | Co-expression of heterologous enzymes, farnesyl diphosphate synthases (FDPSs), and sesquiterpene synthase (ex. Citrus sinensis valencene synthase CsTPS1, Artemisia annua terpene synthase, amorpha-4,11-diene synthase ADS) in mitochondria and cytosol improved the production of valencene and amorphadiene | W303-1A (MATa, ade2-1 trp1-1 leu2-3, 112 his3-11, 15 ura3-1) mBDXe (a uracilauxotroph derivative of strain BDX, Lallemand, Rexdale, Ontario, Canada) | [31] | |
| Casbene (an anti-fungal diterpene) | Genes of putative Casbene synthases from different Euphorbiaceae species were isolated and applied for production of diterpenes. Maximum concentration of Casbene was 31 mg/l | BY4742 (MATα his3D1 leu2D0 lys2D0 ura3D0) | [32] | |
| Cinnamoyl anthranilates | Twenty-six different cinnamoyl anthranilates molecules were produced by co-expressing a 4-coumarate/CoA ligase (4CL, EC 6.2.1.12) from Arabidopsis thaliana and a hydroxycinnamoyl/benzoyl-CoA/anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT, EC 2.3.1.144) from Dianthus caryophyllus | BY4742 (MATα his3D1 leu2D0 lys2D0 ura3D0) | [33] | |
| Cubebol | Overexpression of GFTpsC (a sesquiterpene synthase isolated from Citrus paradisi and encoding for a cubebol synthase) with integration of tHMG1 into genome and reduction of ERG9 gene expression produced cubebol up to 10 mg/l | CEN.PK113-5D (MATa MAL2-8c SUC2 ura3-52) | [34] | |
| Eicosapentaenoic acid (EPA) | Five heterologous fatty acid desaturases and an elongase were identified by a BLAST search and assayed their substrate preferences activity. Without supplement of fatty acids, EPA/ARA were produced | CEN.PK113-5D (MATa MAL2-8c SUC2 ura3-52) | [35] | |
| Farnese and geranyl geraniol | ERG9 deletion and overexpression of two isozymes of HMGCoA reductases (HMG1 and HMG2) was implemented in a host strain with overexpression of diverse FPP synthases and GGPP synthases | FL100 (MATa, ATCC: 28383) | [36] | |
| l-ascorbic acid | About 100 mg of l-ascorbic acid per liter was produced by overexpression of d-arabionono-1,4-lactose oxidase from S. cerevisiae and l-galactose dehydrogenase from Arabidopsis thaliana |
GRF18U (MATα his3 leu2 ura3; NRRL Y-30320) W303 1B (MATα ade2-1 his3-11,15 leu2-3,112 trp1-1 ura3-1 can1-100) |
[37] | |
| Linalool | Overexpression of Clarkia breweri linalool synthase gene (LIS) in wine strain T73 showed higher levels of linalool than conventional laboratory strains. Combining with deregulation of HMG-CoA reductase improved linalool yield | BQS252 (MATa ura3-52 (derivative of FY1679)) | [38] | |
| Methylmalonyl-coenzyme A | Polyketide precursor (Methylmalonyl-CoA) pathway was constructed by introducing propionyl-CoA carboxylase and malonyl/methylmalonyl-CoA ligase from Streptomyces coelicolor |
InvSC1 (MATa, his3delta1, leu2, trp1-289, ura3-52 (Invitrogen, Carlsbad, CA, USA)) BJ5464 (MATα, ura3-52, trp1, leu2-delta1, his3-delta200, pep4::HIS3, prb1-delta1.6R, can1, GAL). |
[39] | |
| Patchoulol | A physical fusion between native (farnesyl diphosphate synthase) and heterologous enzymes (patchoulol synthase of plant origin, Pogostemon cablin was successfully applied to produce patchoulol, 25 mg/l | CEN.LA100 (MATa/MATα ERG20/erg20::hph MAL2-8c/MAL2-8c SUC2/SUC2 ura3-52/ura3-52) | [40] | |
| Resveratrol | Co-expression of the coenzyme-A ligase-encoding gene (4CL216) from a hybrid poplar and the grapevine resveratrol synthase gene (vst1) from Vitis vinifera with supplement of p-coumaric acid produced resveratrol, 1.45 mg/L | FY23 (MATa ura3-52 trplA63 leu2A1) | [41] | |
| Vanillin | Knock-out targets, PDC1 and GDH1, suggested by in silico metabolic model was applied and production of vanillin was improved up to fivefold | X2180-1A (MATa his3D1 leu2D0 met15D0 ura3D0 adh6::LEU2 bgl1::KanMX4 PTPI1::3DSD [AurC]::HsOMT [NatMX]::ACAR [HphMX]) | [42] | |
| Se-methylselenocysteine | Combination of metabolic (codon optimization of heterologous selenocysteine methyltransferase) and bioprocess (tuning carbon-and sulfate-limited fed-batch) engineering achieved 24-fold increase in Se-methylselenocysteine production | CEN.PK113-7D (MATa MAL2-8C SUC2) | [43] | |
| Non-ribosomal peptides | Separated non-ribosomal peptide synthetase modules with compatible communication-mediating domains showed functional interaction, which meant that new module combinations could produce novel non-ribosomal peptides | CEN.PK113-11C (MAT a MAL2-8c SUC2 ura3-52 his3-D1) | [44] | |
| Protein drugs | Insulin-like growth factor 1 (fhlGF-1) | Inactivation of GAS1 increased the yield of human insulin-like growth factor1, from 8 to 55 mg/l | GcP3 (MAT a pep4-3 prb1-1122 ura3-52 leu2 gal2 cir°) | [45] |
| Glucagon | Disruption of YPS1 encoded aspartic protease increased glucagon, 17.5 mg/l | SY107 (MATα YPS1 Δtpi::LEU2 pep4-3 leu2 Δura3 cir +) | [46] | |
| Single-chain antibodies (scFv) | Production of an anti-transferrin receptor single-chain antibody (OX26 scFv) was optimized by adjusting expression temperature and gene dosage and final yield was 0.5 mg/l | BJ5464 (MATa ura3-52 trp1 leu2D1 his3D200 pep40HIS3 prb1D1.6R can1 GAL) | [47] | |
| Hepatitis surface antigen (HBsAg) | Glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter of Pichia pastoris was used for HBsAg production and final yield was 19.4 mg/l | INVSc1 (MATa his3D1 leu2 trp1-289 ura3-52) | [48] | |
| Parvovirus B19 VP2 | The major-capsid protein VP2 of Parvovirus B19 produced in S. cerevisiae showed similar properties to native virus or produced by baculovirus system in size, molecular weight, and antigenicity. The yield was 400 mg/l | HT393 (MATa leu2-3 leu2-112 ura3Δ5 prb1-1 prc1-1 pra1-1 pre1-1) | [49] | |
| Epidermal growth factor (EGF) | O-glycosylation pathway was constructed by introduction of GFR (GDP-fucose transporter), POFUT1 (O-fucosyltransferase 1), manic fringe gene (β1,3-N-acetylglucosaminyltransferase) from human and MUR1 (GDP-mannose-4,6-dehydratase), AtFX/GER1(GDP-4-keto-6-deoxy-mannose-3,5-epimerase/4-reductase) from Arabidopsis thaliana producing O-glycosylated EGF protein |
W303-1A (MATa leu2-3,112 his3-11,15 ade2-1 ura3-1 trp1-1 can1-100) W303-1B (MATα leu2-3,112 his3-11,15 ade2-1 ura3-1 trp1-1 can1-100) |
[50] | |
| Immunoglobulin G | Leader peptides for the enhanced secretion of proteins constructed by directed evolution allowed for a 180-fold increase in secretion of full-length, functional, glycosylated human IgG | BJ5464a (MATα ura3-52 leu2~1 his3~200 pep4::HIS3 prb1~1.6Rcan1 GAL) | [51] | |
| Hepatitis B virus surface antigen (HBsAg) | The yield of S domain of hepatitis B virus surface antigen (sHBsAg) was increased by co-expression of disulfide isomerase (PDI1) with adjusting fermentation mode | S. cerevisiae 2805 (MATα pep4::HIS3 prb-Δ1.6 his3 ura3-52 gal2 can1) | [52] | |
| L1 protein of human papillomavirus (HPV) type16 | Optimization of the secondary structure of HPV16 L1 mRNA increased the expression level of that protein up to fourfold than of wild-type | S. cerevisiae 2805 (MATα pep4::HIS3 prb-Δ1.6 his3 ura3-52 gal2 can1) | [53] |