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Table 1 Production of nutraceuticals in engineered microorganisms from simple carbon sources

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]
  1. aDCW represents EPA content at dry cell weight