Table 1.
Dynamic metabolic control in metabolic engineering.a
| Hostb | Control Strategyc | Sensing signal | Actuation leveld | Target pathwaye | Performance improvement | Reference | |
|---|---|---|---|---|---|---|---|
| 1 | EC | TS, CM | ACP | TX | Terpenoid (lycopene) | 18-fold (yield) | Farmer and Liao (2000) |
| 2 | EC | CM | Fatty acyl-CoA | TX | Fatty acid derivative (FAEE) | 2-fold (titer) | Zhang et al. (2012) |
| 3 | SC | TS | Glucose | TX | Terpenoid (α-santaleane) | 1.5-fold (titer) | Scalcinati et al. (2012) |
| 4 | EC | TS | Temperature | TX | Lactate | 1.3-fold (titer) | Zhou et al. (2012) |
| 5 | EC | CM | Stress (FPP) | TX | Terpenoid (amorphadiene) | 2-fold (titer) | Dahl et al. (2013) |
| 6 | EC | CM | Malonyl-CoA | TX | Free fatty acid | 2.1-fold (titer) | Xu et al. (2014) |
| 7 | EC | TS | QS (AHL) | TX | 1,4-butanediol | No static control | Liu and Lu (2015) |
| 8 | EC | CM | Malonyl-CoA | TX | Free fatty acid | 1.3-fold (titer) | Liu et al. (2015b) |
| 9 | EC | TS | QS (AHL) | TX | Isopropanol | 3.7-fold (titer); 3.1-fold (yield) | Soma and Hanai (2015) |
| 10 | SC | TS | QS (pheromone) | RNAi | Aromatic (PHBA) | 2.4-fold (titer) | Williams et al. (2015) |
| 11 | SC | TS | Glucose | TX | Terpenoid (carotenoid) | 1.3-fold (content) | Xie et al. (2015) |
| 12 | SC | CM | Ergosterol | TX | Terpenoid (amorphadiene) | 5-fold (titer) | Yuan and Ching (2015) |
| 13 | CG | TS | Lysine | TL | Lysine | 1.9-fold (yield) | Zhou and Zeng (2015a, b) |
| 14 | SC | TS, CM | Glucose, Malonyl-CoA | TX | 3-HP | 10-fold (titer) | David et al. (2016) |
| 15 | EC | TS | Glucose, hydroxycinnamoyl-CoA | TX | Vanillic acid | 5-fold (titer) | Lo et al. (2016) |
| 16 | EC | TS | Glucose, fatty acyl-CoA | TX | Fatty acid derivative (FAEE) | 2.4-fold (titer) | |
| 17 | EC | TS, CM | Stress (FPP) | TX | Terpenoid (zeaxanthin) | 2-fold (content); 2.1-fold (titer) | Shen et al. (2016) |
| 18 | EC | PB | Fatty acyl-CoA | TX | Free fatty acid | 4.5-fold (titer); 2.5-fold (yield) |
Xiao et al. (2016) |
| 19 | EC | PB | Tyrosine | TX | Tyrosine | 2.6-fold (titer) | |
| 20 | EC | TS | QS (AHL) | TX | MI MI derivative (Glucaric acid) Shikimate |
5.6-fold (titer); 4-fold (titer) ND to 105 mg/L |
Gupta et al. (2017) |
| 21 | EC | TS | QS (AHL), Phase | TX | PHB | 2.9-fold (content) | He et al. (2017) |
| 22 | EC | TS | Dissolved oxygen | TX | Lactate 2,3-butanediol 1,3-propanediol |
No static control | Hwang et al. (2017) |
| 23 | EC | TS | QS (AHL) | TX | Terpenoid (bisabolene) | 1.4-fold (titer) | Kim et al. (2017) |
| 24 | EC | CM | Ammonium | TX | Cyanophycin | 1.4-fold (titer) | Xiao et al. (2017) |
| 25 | AR | TS | Low pH | TX | Itaconate | 6-fold (titer) | Yin et al. (2017) |
| 26 | EC | TS, CM | QS (AHL), MI | TX | MI derivative (glucaric acid) | 4-fold (titer) | Doong et al. (2018) |
| 27 | EC | TS | Temperature | TX | Itaconate | 1.5-fold (titer); 1.9-fold (productivity) |
Harder et al. (2018) |
| 28 | STR | TS | Cell phase | TX | Polyketide (actinorhodin) Polyketide (oxytetracycline) |
1.3-fold (titer) 9.1-fold (titer) |
Li et al. (2018) |
| 29 | SC | TS | Glucose | TX | 3-HP | 1.7-fold (titer) | Maury et al. (2018) |
| 30 | BS | CM | GlcN6P | TX | GlcNAc | 2-fold (titer) | Niu et al. (2018) |
| 31 | SC | TS, CM | Ergosterol, glucose | PD, TX | Terpenoid (linalool) Terpenoid (limonene) |
44-fold (titer) ND to 76 mg/L |
Peng et al. (2018) |
| 32 | EC | TS | MA | TX, asRNA | Aromatic (MA) | 4.7-fold (titer) | Yang et al. (2018) |
| 33 | SC | TS | Light | TX | Isobutanol 2-MBOH |
4-fold (titer) 3-fold (titer) |
Zhao et al. (2018) |
| 34 | CG | CM | Isoleucine | Attenu-ation | 4-HIL | 2.3-fold (titer); 2.5-fold (yield) |
Zhang et al. (2018) |
| 35 | BS | TS, CM | QS (Phr60) | TX | Terpenoid (menaquinone-7) | 40-fold (titer) | Cui et al. (2019) |
| 36 | EC | TS | QS (AHL) | TX | Aromatic (naringenin) salicylic acid |
15-fold (titer) 1.8-fold (titer) |
Dinh and Prather (2019) |
| 37 | EC | TS | Phase | PD | Shikimate | 8.5-fold (titer) | Gao et al. (2019) |
| 38 | EC | TS | Oscillator | PD | Xylonate | 2-fold (titer) | |
| 39 | EC | TS | QS (AHL), stress | TX | Terpenoid (oxygenated taxanes) | 2.4-fold (titer) | Glasscock et al. (2019) |
| 40 | EC | PB | 4-HB | TX | Phenol | 1.8-fold (titer) | Guo et al. (2019) |
| 41 | EC | PB | Tyrosine | TX | Phenol | 2.7-fold (titer) | |
| 42 | EC | TS | QS | TX | Aromatic (4-HPAA) | 1.5-fold (titer) | Shen et al. (2019) |
| 43 | EC | PB | Tryptophan | TX | Tryptophan | 1.5-fold (titer) | Wang et al. (2019) |
| 44 | EC | PB | Phenylalanine | TX | Phenylalanine | 1.5-fold (titer) | |
| 45 | EC | TS | Phenylalanine | TX | Phenylalanine | 1.4-fold (titer) | Wu et al. (2019) |
| 46 | EC | TS | QS (AHL) | GS | Xylonate Shikimate |
1.4-fold (titer) 12.3-fold (titer) |
Gao et al. (2020) |
| 47 | EC | PB | 4-HB | TX | PCA | 1.2-fold (titer) | Guo et al. (2020) |
| 48 | EC | TS | QS (AHL) | TX | PHB ALA |
6-fold (titer) 12-fold (titer) |
Gu et al. (2020) |
| 49 | EC | TS | Vanillin | TX | Aromatic (vanillin) | 1.2-fold (titer) | Liang et al. (2020) |
| 50 | YL | CM, PB | Malonyl-CoA, naringenin | TX, CRISPRi | Aromatic (naringenin) | 1.8-fold (titer) | Lv et al. (2020) |
| 51 | STR | TS | QS (GBL) | TX | Polyketide (rapamycin) | 6.6-fold (titer) | Tian et al. (2020) |
| 52 | BS | CM | GlcN6P | TX, CRISPRi | GlcNAc | 1.6-fold (titer) | Wu et al. (2020) |
| 53 | EC | PB | Tryptophan | TX | Tryptamine | 2.1-fold (titer) | Wang et al. (2020) |
Examples using only traditional inducers are excluded. Examples are sorted by the year when the literature was published. In one literature, if a sensor-actuator system is applied to multiple pathways, these applications are considered as one example of dynamic metabolic control.
Host abbreviations: EC, Escherichia coli; SC, Saccharomyces cerevisiae; CG, Corynebacterium glutamicum; AR, Aspergillus niger; BS, Bacillus subtilis; STR, Streptomyces species; YL, Yarrowia lipolytica.
Strategy abbreviations: TS, two-stage metabolic control; CM, continuous metabolic control; PB, population behavior control.
Actuation level abbreviations: TX, transcription; TL, translation; PD, protein degradation; asRNA, antisense RNA; GS, genetic sequence; CRISPRi, CRISPR interference; RNAi, RNA interference.
Other abbreviations: QS, quorum sensing; AHL, N-acyl homoserine lactones; GBL, γ-butyrolactones; ACP, acetyl phosphate; MI, myo-inositol; MA, muconic acid; FAEE, fatty acid ethyl ester; PHBA, para-hydroxybenzoic acid; 3-HP, 3-hydroxypropionic acid; 4-HPAA, 4-hydroxyphenylacetic acid; PHB, poly-β-hydroxybutyrate; GlcN6P, glucosamine-6-phosphate; GlcNAc, N-acetylglucosamine; 4-HIL, 4-hydroxyisoleucine; 2-MBOH, 2-methyl-1-butanol; 4-HB, 4-hydroxybenzoate; PCA, protocatechuic acid; ALA, 5-aminolevulinic acid; ND, not detectable.