Table 1 The synthesis of isoflavones in engineered yeast

p-HCA

S. cerevisiae

Overexpressing genes in the shikimate and AAA pathways; introducing the PHK pathway and ARO4^K229L, ARO7^G141S mutants; knocking out PDC5, ARO10, GPP1 and GAL7/1/10

Glucose

12.5 g/L

(Bioreactor)

p-HCA

Y. lipolytica

Increasing the copy number of TAL; redesigning the shikimate pathway

Glucose

1035.5 ± 67.8 mg/L

(Shake flask)

Liquiritigenin

S. cerevisiae

Introducing exogenous PAL, C4H, 4CL, CHS, CHR, and CHI

Glucose

1.0 µM/L

(Bioreactor)

Liquiritigenin

Y. lipolytica

Screening the optimal genes for producing five heterologous liquiritigenin compounds: PAL, 4CL, CHS, CHR and CHI; fusing the CHS and CHR; optimizing the length of the promoter

p-HCA

62.4 mg/L

(Shake flask)

Naringenin

S. cerevisiae

Introducing the PHK and aldehyde dehydrogenase pathways; overexpressing genes in the shikimate, AAA, and malonyl-CoA synthesis pathways; introducing ARO4^K229L, ACC1^S659A/S1157A and ARO7^G141S mutants; introducing exogenous PAL、TAL、C4H、4CL、CHS、CHI and CPR; knocking out PDC5 and ARO10; regulating subcellular carbon flux

Glucose

3420.6 mg/L

(Bioreactor)

Naringenin

Y. lipolytica

Modulating the shikimate and AAA pathways; introducing a mutant Y. lipolytica allele.

Glucose

898 ± 19 mg/L

(Bioreactor)

Genistein

S. cerevisiae

Fusion expression of C4H and 4CL; introducing exogenous CHS, CHI, 2-HIS, HID, and CPR; overexpressing HEM2, HEM3, INO2, STB5, and EcyjfB; knocking out ROX1, OPI1, HMX1, PAH1, GAL1/7/10, and ELP3; supplementing 5-ALA; replacing the FAS1 promoter

p-HCA

33.7 mg/L

(Shake flask)

Daidzein

S. cerevisiae

Fusion expression of C4H and 4CL; introducing exogenous CHS, CHR, CHI, 2-HIS, HID, and CPR; overexpressing HEM2, HEM3, INO2, STB5, and EcyjfB; knocking out ROX1, OPI1, HMX1, PAH1, GAL1/7/10, and ELP3; supplementing 5-ALA; replacing the FAS1 promoter

p-HCA

85.4 mg/L

(Shake flask)

Medicarpin

S. cerevisiae

Introducing exogenous 2-HIS, CPR, I4’OMT, HID, I2’H, IFR, VR, and PTS; increasing the copy number of VR and PTS

Liquiritigenin

2.05 ± 0.72 mg/L

(Shake flask)

Sakuranetin

S. cerevisiae

Overexpressing genes in the shikimate and AAA pathways; introducing ARO4^K229L, ACC1^S659A/S1157A and ARO7^G141S mutants; introducing exogenous 4CL, CHS, CHI; increasing the copy number of PAL, TAL, and CHS; knocking out ARO10, PDC5, and YPL062W

Glucose

158.65 mg/L

(Bioreactor)

Xanthohumol

S. cerevisiae

Overexpressing genes in the shikimate pathway; introducing exogenous TAL, 4CL and CHS, introducing ARO4^K229L, ARO7^G141S and ERG20^N127W mutants; knocking out ARO10; replacing ACC1 promoter; overexpressing MVA pathway genes

Glucose

142 µg/L

(Shake flask)

Icariin

S. cerevisiae

Overexpressing ACC1 as well as genes in the shikimate, AAA, and MVA pathways; introducing ARO4^K229L and ARO7^G141S mutants; introducing exogenous 4CL, CHS and CHI

Glucose

130 µg/L

(Shake flask)

Phloretin

S. cerevisiae

Overexpressing genes in the AAA pathway; introducing exogenous 4CL, CHS, ACS, ACC1, and aldehyde dehydrogenase (ADH2, ALD6) genes

Glucose

619.5 mg/L

(Bioreactor)

Homoeriodictyol

S. cerevisiae

Introducing exogenous 4CL, CHS and CHI; fusion expression of CHS and CHI; overexpressing ACC1and acetyl-CoA synthetase (ACS) genes; knocking out phenylacrylic acid decarboxylase (PAD1) and ferulic acid decarboxylase (FDC1) genes

p-HCA

3.2 mmol/L

(Bioreactor)

Eriodictyol

Y. lipolytica

Screening efficient heterologous TAL, 4CL, CHS and CHI key enzyme genes; optimizing promoter strategies; increasing the flux of shikimate pathway; promoting fatty acid β-oxidation; increasing the copy number of synthetic pathway genes

Glucose

6.8 g/L

(Bioreactor)

Scutellarin

Y. lipolytica

Screening efficient TAL, 4CL, CHS, and CHI from different sources; introducing feedback-resistant AroG* and TyrA* from E. coli; disrupting the key gene MHY1 that controls cell morphology

Glucose

703.01 ± 4.83 mg/L

(Shake flask)