From: Metabolic engineering of microbial cell factories for production of nutraceuticals
Product | Titer (mg/L) | Carbon source | Platform organism | Medium, fermentation type and parameters | References |
---|---|---|---|---|---|
Polyunsaturated fatty acids | |||||
 α-Linolenic acid | 1400 | Glucose | Y. lipolytica L36DGA1 | YSC medium contained 80 g/L glucose; a pulse of 80 g glucose was added at 72 h/fed-batch 2 L bioreactor, 20 °C | [28] |
 EPA | 56.6% in total lipids with 15% DCWa 50% in total lipids with 25% DCWa | Glucose | Y. lipolytica ATCC 20362 Y. lipolytica Y4305 | Nitrogen-rich medium contained 20 g/L glucose for the first stage fermentation, and nitrogen-limited medium contained 80 g/L glucose for the second stage fermentation/two-stage flask, 30 °C Two-stage 2 L bioreactor, 30 °C | [4] [22] |
 DHA | 2.4 (5% of total fatty acids) | Complex media | E. coli DH5α | LB medium was supplemented with 1 mg/L cerulenin/flask, 15 °C after 1 mM IPTG induction | [32] |
 DHA | 5.6% in total lipids | Glucose | Y. lipolytica Y4305 | Cells were grown in MM medium containing 20 g/L glucose for 48 h, then transferred to HGM medium containing 80 g/L glucose for additional 72 h fermentation/two-stage fermentation, 30 °C | [31] |
Polyphenols | |||||
 Naringenin | 100.64 | Glucose | E. coli BL21 (DE3) | MOPS medium contained 5 g/L glucose and 4 g/L NH4Cl/flask, 30 °C | [42] |
 Naringenin | 54.4/112.9 | Glucose | S. cerevisiae CEN.PK | Synthetic medium contained 20 g/L glucose and 10 g/L (NH4)2SO4/flask or batch 2 L bioreactor, 30 °C | [43] |
 Naringenin | 21 | Xylose | E. coli BW25113 and S. cerevisiae CEN.PK2-1C | Synthetic fermented medium contained 40 g/L xylose, 5 g/L yeast extract and inorganic salt/flask, 30 °C | [44] |
 Resveratrol | 416 (glucose)/531 (ethanol) | Glucose or ethanol | S. cerevisiae CEN.PK102-5B | Medium contained 40 g/L glucose (for batch phase), trace metals and vitamin solutions; 16 g/L glucose or 17 g/L ethanol for feeding/fed-batch 1 L bioreactor, 30 °C | [47] |
 Resveratrol | 812 (glucose)/755 (ethanol) | Glucose or ethanol | S. cerevisiae CEN.PK102-5B | Medium contained 40 g/L glucose (for batch phase), trace metals and vitamin solutions; 88 g/L glucose or 79 g/L ethanol for feeding/fed-batch 1 L bioreactor, 30 °C | [48] |
 Resveratrol | 22.6 | Glycerol | E. coli W3110 coculture | M9 medium contained 0.3 mM l-phenylalanine and 10 g/L glycerol/batch 1 L bioreactor, 30 °C | [49] |
 Kaempferol | 27 | Glucose | S. cerevisiae CEN.PK102-5B | Synthetic feed-in-time medium contained vitamins, dextrose polymer and enzyme minx/96-deep well plate, 30 °C | [54] |
 Quercetin | 20 | ||||
 Afzelechin | 41 | Glycerol | E. coli BL21star™(DE3)ΔsucCΔfumC (upstream strain) and BL21star™(DE3) (downstream strain) | Initial AMM medium contained 20 g/L glycerol; feed solution contained 2 × MOPS mix with 250 g/L glycerol/fed-batch bioreactor, 30 °C | [56] |
Carotenoids | |||||
 Lycopene | 1230 | Glycerol | E. coli BL21(DE3) | M9 medium contained 40 g/L glycerol; engineered strain consumed around 130 g/L glycerol/fed-batch 150 L bioreactor, 30 °C | [71] |
 Lycopene | 2370 | Glucose or ethanol | S. cerevisiae CEN.PK2-1D | Feeding solution contained 500 g/L glucose and 15 g/L yeast extract for the first stage fermentation, and ethanol was used for the second stage fermentation/Two-stage fed-batch 7 L bioreactor, 30 °C | [64] |
 β-Carotene | 3200 | Glycerol | E. coli BL21(DE3) | Optimized medium contained 20 g/L glycerol; 400 g/L glycerol was fed at a rate of 3 g/L/h/fed-batch 5 L bioreactor, 34 °C after IPTG induction | [70] |
 β-Carotene | 2100 | Glycerol | E. coli ATCC 8739 | Synthetic medium contained 10 g/L glycerol; 500 g/L glycerol was fed at a rate of 20 mL/h/fed-batch 7 L bioreactor, 37 °C | [72] |
 β-Carotene | 4000 | Glucose | Y. lipolytica MYA2613 | Optimized medium with the C/N ratio at 3:1.5 for the first stage fermentation, and 600 g/L glucose was used for the second stage fermentation/Two-stage fed-batch 2 L bioreactor, 30 °C | [66] |
 β-Carotene | 6500 | Glucose | Y. lipolytica Po1d | YPD medium contained 20 g/L yeast extract, 40 g/L peptone and 5 g/L glucose; additional glucose was added after 6 h at a rate of 6 g/h/fed-batch 5 L bioreactor, 28 °C | [65] |
Astaxanthin | 432.8 (7.12 mg/g DCW) | Glycerol | E. coli W3110 | Modified medium contained 30 g/L glucose and 5 g/L yeast extract (for batch phase); glycerol concentration was maintained at 0–2 g/L for feeding; 0.5 mM IPTG was added when OD600 reached 30–40/fed-batch 5 L bioreactor, 30 °C | [68] |
Astaxanthin | 217.9 (13.8 mg/g DCW) | Glucose | S. cerevisiae BY4742 | YPD medium contained 20 g/L glucose; glucose feeding was controlled below 2 g/L and 30 g yeast extract was added every 12 h/fed-batch 5 L bioreactor, 30 °C | [67] |
Astaxanthin | 54.6 (3.5 mg/g DCW) | Glucose | Y. lipolytica GB20 | YPD medium contained 80 g/L glucose/microtiter plate, 30 °C | [69] |
Non-proteinogenic amino acid | |||||
 β-Alanine | 32300 | Glucose | E. coli W3110 | Synthetic medium contained 20 g/L glucose and 9 g/L (NH4)2SO4; 240 g/L glucose was consumed/fed-batch 6.6 L bioreactor, 37 °C | [85] |
 GABA | 4800 | Glucose | E. coli BW25113 | M9 medium contained 20 g/L glucose/flask, 37 °C | [87] |
 GABA | 39000 | Glucose | C. glutamicum ATCC 13032 | GP1 medium contained 100 g/L glucose and 50 μg/L biotin; 498 g glucose was consumed/fed-batch 5 L bioreactor, 30 °C | [88] |