Introduction
Discovery of artemisinin
Biosynthesis of artemisinin and expression pattern of artemisinin biosynthetic genes in A. annua
Mode of action of artemisinin
Enhancement of artemisinin production
Plant breeding technologies
Overexpression of genes involved in artemisinin biosynthetic pathway
Direct or indirect upregulation of artemisinin biosynthesis
Heterologous production
Host | No. | Transgenes or modifications | Product | Yield | References |
---|---|---|---|---|---|
N. benthamiana
| 1 |
P
35S
-tHMGR-FPS-ADS, P
35S
-CYP71AV1
| Artemisinic acid 12-β-diglucoside | 39.5 mg/kg FW | [106] |
Tobacco chloroplasts | 2 |
P
rrn16S
-atoB-HMGS-HMGR-MK-PMK-MVD1, P
psbA
-E. coli
IDI-FPS-ADS-CYP71AV1-AaCPR
| Artemisinic acid | 0.1 mg/g FW | [107] |
E. coli
| 3 |
P
lac
-MevT
a, P
lac
-MBIS
b, P
trc
-ADS
| Amorpha-4,11-diene | 24 mg/L | [109] |
4 | Same as 3 but overlaid with dodecane | Amorpha-4,11-diene | 500 mg/L | [110] | |
5 |
P
BAD
-MevT, P
BAD
-tHMGR1
| Mevalonate | Threefold from CTc
| [111] | |
6 |
P
lacUV5
-MevT (codon opt.)-MBIS, P
trc
-ERG12 (codon opt.)-ADS
| Amorpha-4,11-diene | 293 mg/L | [112] | |
7 |
P
lacUV5
-MevT (codon opt.) with HMGS and HMGR from S. aureus, P
lac
-MBIS, P
lac
-ADS
| Amorpha-4,11-diene | 27.4 g/L | [113] | |
8 |
P
BAD
-dxs-IDI-ispDF, ADS with Δpts and optimized medium | Amorpha-4,11-diene | 182 mg/L | [114] | |
9 |
P
TM2
-galP-glk, P
T7
-dxs-IDI-ispA-ADS
| Amorpha-4,11-diene | 201.2 mg/L | [115] | |
10 |
AcrB, TolC (x2), ADS (codon opt.) | Amorpha-4,11-diene | 404.83 mg/L | [116] | |
11 |
P
BAD
-dxs-IDI-ispDF, P
araBAD
-ADS, P
TM1
-macAB-TolC
| Amorpha-4,11-diene | ~30 mg/L/OD | [117] | |
12 | Same as 3 with CYP71AV1 (codon opt., engineered N-terminal transmembrane)-AaCPR
| Artemisinic acid | 105 mg/L | [118] | |
13 | Same as 12 but replaced CYP71AV1 with P450
BM3
| Artemisinic-11S,12-epoxide | 250 mg/L | [119] | |
S. cerevisiae
| 14 |
P
GAL1
-ADS
| Amorpha-4,11-diene | 600 μg/L | [120] |
15 |
P
GAL1
-tHMGR P
GAL1
-upc2-1 erg9::P
MET3
-ERG9 P
GAL1
-tHMGR P
GAL1
-ERG20, P
GAL1
-ADS P
GAL10
-CYP71AV1 P
GAL1
-AaCPR
| Artemisinic acid | 100 mg/L | ||
16 | Same as 15 with optimized culture condition | Artemisinic acid | 2.5 g/L | [123] | |
17 |
gal80Δ::nat
r
MAT a erg9Δ∷kan
r
P
MET3
-ERG9, leu2-3,112∷HIS P
GAL1
-MVD1 P
GAL10
-ERG8 his3Δ1∷HIS P
GAL1
-ERG12 P
GAL10
-ERG10ade1Δ∷P
GAL1
-tHMG1 P
GAL10
-IDI1 ADE1 ura3-52∷P
GAL1
-tHMG1 P
GAL10
-ERG13 URA3trp1-289∷P
GAL1
-tHMG1 P
GAL10
-ERG20 TRP1 [pAM322] | Amorpha-4,11-diene | 41 g/L | [124] | |
18 | Same as 17. but replaced gal80Δ::nat
r
with gal1Δ gal7Δ gal10Δ::hphA
| Amorpha-4,11-diene | 37 g/L | [124] | |
19 |
gal1Δ,gal10Δ,gal7Δ::P
GAL3
-CPR1natA, erg9Δ::dsdAP
CTR3
- ERG9, leu2-3,112::kanAP
GAL7
-AaCYB5P
GAL1
-ERG19P
GAL10
- ERG8, ade1Δ::P
GAL1
-tHMG1P
GAL10
-IDI1_ADE1, his3Δ1::hphAP
GAL7
-AaALDH1P
GAL1
-ERG12P
GAL10
-ERG10, ura3-52:: P
GAL1
-tHMG1P
GAL10
-ERG13hisG, trp1-289:: P
GAL1
- tHMG1P
GAL10
-ERG20TRP1, ndt80Δ::P
TDH1
-HEM1HIS3PPGK1-CTT1, gal80Δ::URA3P
GAL7
-AaADH1, [pAM552: 2μ-LEU2d P
GAL1
-ADS P
GAL10
-CYP71AV1] | Artemisinic acid | 25 g/L |