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. 2021 Mar 26;14(4):295. doi: 10.3390/ph14040295

Table 3.

Terpene titers obtained in S. cerevisiae and respective fermentation strategies.

Group Product Titer (mg/L) Carbon Source Nitrogen Source pH °C Aeration
/Agitation		 Dissolved Oxygen Inoculum Size Feeding
Strategy		 Operation Mode References
Monoterpenes Limonene 1.48 2 g/L glucose and
18 g/L galactose 		(NH4)2SO4 - 30 200 rpm - 1 OD = 0.05 - Shake-flask [80]
(-)-Limonene 0.49 20 g/L glucose and
20 g/L galactose		 (NH4)2SO4 - 30 300 rpm - OD = 0.05 - Shake-flask [81]
Limonene 918 20 g/L initial glucose and 10 g/L pure ethanol Tryptone, Yeast extract - 30 250 rpm - OD = 0.2 Pure ethanol Fed-Batch in shake flask [72]
Geraniol 5 10 g/L glucose (NH4)2SO4 - 28 - - 2.5% - Shake-flask [88]
Geraniol 293 20 g/L initial glucose and then fed solution (glucose and other nutrients) (NH4)2SO4 6.0 30 600 rpm/1 vvm >30% OD = 0.15 Fed solution (glucose and other nutrients) feeding by
controlling the specific feed rate to 0.1 h−1 		Fed-Batch [69]
Geraniol 1680 Initial YPD medium, then glucose and ethanol Yeast extract, Peptone 5.7 30 300–500 rpm
/2 vvm		 >30% 10% Glucose feeding under 1 g/L and ethanol feeding under 5 g/L Fed-Batch (Carbon restricted) [73]
Geraniol 1690 Initial 20 g/L glucose then pure ethanol feeding (NH4)2SO4 5.0 30 600 rpm/1 vvm >30% OD = 0.2 400 g/L pure ethanol at 0.1 L/h feed rate Fed-Batch [69]
Sabinene 17.5 20 g/L glucose
20 g/L galactose and
10 g/L raffinose		 (NH4)2SO4 - - - - - - - [70]
(S)-linalool 0.26 20 g/L glucose Yeast extract 5.5 30 400 rpm/2 vvm - OD = 0.05 - Batch Bioreactor [68]
Sesquiterpenes Bisabolone 900 2 g/L glucose and
18 g/L galactose		 Yeast extract, peptone - 30 180 rpm - OD = 0.05 - Shake-flask [66]
Bisabolone 5200 Initial 15 g/L glucose (NH4)2SO4 5.0 30 0.7 L/min air - OD = 0.1 Constant feed rate with pH rise trigger Fed-batch [76]
Nerolidol 336.5 20 g/L sucrose (NH4)2SO4 - 30 180 rpm - OD = 0.2 - Two-phase flask cultivation [19]
Nerolidol 5500 Initial 20 g/L glucose, and then sucrose feeding (NH4)2SO4 5.0 - 300–600 rpm/1.58–3.16 L/h air 30% OD = 0.2 Exponential feeding (3 mM sucrose/g biomass/h) with specific increasing rate (0.05 h−1 then 20 g/L sucrose pulse feeding by DO spikes Fed-Batch [84]
Valerenic acid 4 20 g/L galactose and 2 g/L dextrose Yeast extract, Peptone - 30 200 rpm - - - Milliliter plates [82]
Polpunonic acid 1.4 20 g/L galactose and 10 g/L raffinose - - 30 150 rpm - - - Shake-flask [20]
Amorpha-4,11-diene >4000 Initial 20 g/L glucose then pure ethanol pulse feeding, 0.25 g/L methionine as inducer (NH4)2SO4 5.0 30 1 L/min air 40% - Ethanol pulse feed (10 g/L), Off-gas CO2 evaluation rate control Fed-Batch [60]
Artemisinic acid 25,000 Initial 20 g/L glucose then pure ethanol pulse feeding, 0.25 g/L methionine as inducer (NH4)2SO4 5.0 30 1 L/min air 40% - Etanol pulse (10 g/L) feed, stir rate control Fed-Batch [27]
Patchoulol 467 Initial glucose (25 g/L) feeding, Feeds: (1) Sole glucose feeding (2) glucose/glycerol feeding, (3) Sole ethanol feeding (NH4)2SO4, Peptone. Yeast extract 5.5 30 200–500 rpm/1–2 vvm - 14% carbon-source (glucose) controlled
three-stage fermentation		 Fed-Batch [22]
Zerumbone 40 Initial 20 g/L glucose, then feed solution (glucose, other nutrients and ingredients) Peptone. Yeast extract 5.5 30 300–600 rpm/2 vvm >30% 5% Fed rate solution (glucose and other nutrients, ingredients) of 2 mL/min control by DO and pH rise trigger Fed-Batch [77]
α-humulene 1700 Initial 20 g/L glucose, then feed solution (glucose, other nutrients and ingredients) Peptone. Yeast extract 5.5 30 300–600 rpm/2 vvm >30% 10% Fed rate solution (glucose and other nutrients, ingredients) of 2 mL/min control by DO and pH rise trigger Fed-Batch [4]
α-santalene 0.036 Cmmol (g/biomass/h) Initial 10 g/L glucose and continuous glucose and dodecane feeding (NH4)2SO4 5.0 30 600 rpm/1 vvm >30% 2 Xi = 1 g/L Two phase feeding (organic phase and 10 g/L glucose), dilution rates of 0.05/h and 0.1/h Continuous [61]
Diterpenes Geranylgeraniol 3310 Initial 1 g/L glucose, then sole glucose and glucose/ethanol mix. feeding (NH4)2SO4
corn
steep liquor		 5.5 33 900 rpm/1 vvm - - Glucose (50% wt/v) and then glucose/ethanol (25% wt/v/50% v/v) feeding (rate of 5.8 g/h) Fed-Batch [89]
Miltiradiene 488 Initial 20 g/L glucose, then feed solution(glucose, other nutrients and ingredients) Peptone. Yeast extract 5.5 30 600 rpm/5 L/h air - OD = 0.05 Feed solution (glucose and other nutrients) addition by 5 mL/h feed rate. Fed-Batch [78]
Oxygenated taxanes 33 Initial 40 g/L glucose or 20 g/L xylose (NH4)2HPO4
Yeast extract		 7.0 30 and 22 280–800 rpm/0.5 L/min 30% 1% for E. coli and 2% for S. cerevisiae Pulse feeding by carbon source control (20 g/L of glucose feed when glucose below 20 g/L and 50 g/L xylose feed when xylose conc. below 10 g/L) Fed-Batch (co-culture) [90]
Triterpenes Protopanaxadiol and dammarenediol-II 1189 and 1548 Initial 25 g/L glucose and then glucose feeding (NH4)2SO4 5.5 30 1000 rpm/5 L/min air - OD = 0.5 Fed solution (glucose and other nutrients) addition when ethanol below 0.5 g/L Fed-Batch [79]
β-amyrin 139 Initial 20 g/L glucose and then pulse ethanol feeding (NH4)2SO4 - 30 1 vvm - OD = 0.2 Pulse ethanol (5 g/L) feeding at every 12 h Fed-Batch [71]
β-amyrin 108 Initial 20 g/L dextrose, and then pulse glucose feeding Yeast extract
Peptone		 6.0 30 - - - Pulse glucose (5 mg/L) feeding at every 12 h Fed-Batch [85]
Betulinic acid 182 Initial 50 g/L glucose and then pulse ethanol feeding NH4Cl 6.0 30 1 vvm >30% Xi2 = 0.08 g/L Pulse ethanol (25 g/L) feeding control with DO spikes Fed-Batch [75]
Ginsenoside Rh2 2250 Initial 25 g/L glucose and then glucose feeding Yeast extract
Peptone		 5.0 30 - >30% 11% Fed solution (glucose and other nutrients) addition when ethanol below 0.5 g/L Fed-Batch [35]

1 Initial optical density (OD); 2 Initial biomass (Xi); “-” Not described.