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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