Table 3 The system metabolic engineering strategies on tyrosine pathway for the microbial production of aromatic compounds

4-HPPA derivatives

 Salvianic acid A

4-HPPA

Glucose

E. coli

7.1 g/L

Fed-batch (shake-flask)

Introducing heterologous gene for glucose transport; deleting genes responsible for PEP and precursor consumption, and transcriptional repression; Overexpressing genes in PP and SHK pathway; Replacing genes encoding feedback-sensitive prephenate dehydrogenase and DAHP synthase with resistant ones

[118]

Glucose

E. coli

5.6 g/L

Fed-batch (Fermentor, 5 L)

λ Red homologous recombination of the modules mentioned in previous study along with similar metabolic engineering strategies

[119]

 Rosmarinic acid

4-HPPA

Glucose

E. coli

0.13 g/L

Batch (shake-flask)

Inserting LDH, HPAH and RAS-coding genes in l-TYR over-producing strain

[123]

L-TYR derivatives

 Tyrosol

4-HPPA

Glucose

E. coli

0.573 g/L

Batch (shake-flask)

Introducing gene encoding pyruvate decarboxylase (PDC) from S. cerevisiae; deleting genes in competing pathways to modulate flux towards 4-HPPA

[125]

l-TYR

Tyrosine

E. coli

1.203 g/L

Whole-cell

Introducing aminotransferase gene into biosynthetic tyrosol pathway

l-TYR

Glucose

E. coli

0.531 g/L

–

Introducing plant gene encoding aromatic amino acid synthase that enables one-step conversion of l-TYR to 4-HPAA

[126]

 Hydroxytyrosol

l-TYR

Glucose

E. coli

0.268 g/L

Batch

Introducing genes encoding feedback-resistant DAHP synthase and prephenate dehydrogenase; Deleting genes responsible for transcriptional repression; Overexpressing genes to modulate carbon flux to DAHP

[129]

 Salidroside

Tyrosol

Glucose/xylose

E. coli–E. coli

6.03 g/L

Fed-batch co-culture (fermentor, 5 L)

Constructing two strains. Deleting genes responsible for PEP consumption, transcriptional repression, competing pathways, GLC consumption in tyrosol producer upstream strain. Deleting genes responsible for XYL and UDP-GLC consumption, and TYR synthesis in downstream salidroside producer strain. Overexpressing genes in PP pathway.

[127]

 p-Coumaric acid

l-TYR

Glucose

S. cerevisiae

1.93 g/L

Fed-batch (well-plate)

Overexpressing genes in SHK pathway a heterologous TAL gene; Deleting genes in competing pathways

[135]

 Caffeic acid

p-coumaric acid

Glucose/glycerol + PHCA

E. coli

2.8 g/L

Whole-cell biocatalysis

Engineering P450 hydroxylase for desired activity to convert p-coumaric acid to caffeic acid

[141]

 p-HS

p-coumaric acid

Glucose

P. putida

17.6 g/L

~ 64

Two-phase decanol system

Deleting gene encoding feruloyl-coenzyme A competes for p-coumarate intermediates; Introducing two heterologous genes, pal and pdc

[152]

 Naringenin

Coumaroyl-CoA

Glucose

E. coli

0.474 g/L

Batch (shake-flask)

According to genome scale model, deleting/down-regulating genes in TCA cycle; overexpressing genes in CCM and malonate assimilation pathway

[160]

 Kaempferol

Naringenin

Glucose

S. cerevisiae

0.026 g/L

Fed-batch (well-plate)

Inserting seven heterologous genes originated from different plants

[170]

 Apigenin

Naringenin

Glucose + l-TYR

E. coli

0.013 g/L

Batch (shake-flask)

Introducing FNS1 gene from Petroselinum crispum into biosynthetic naringenin pathway comprising PAL/TAL, 4CL, CHS, CHI and ACC (encoded by dtsR1 and accBC)

[164]

 Luteolin

Apigenin

Raffinose + caffeic acid

S. cerevisiae

0.002 mg/L

Batch (shake-flask)

Expressing five heterologous genes from plants; Investigating efficiency of native and heterologous CPR

[162]

 Fisetin

Resokaempferol

Glucose

S. cerevisiae

0.002 mg/L

Fed-batch (well-plate)

Inserting nine codon optimized genes originated from plants

[170]

 Quercetin

Eriodictyol

Glucose

S. cerevisiae

0.020 g/L

Fed-batch (well-plate)

Inserting eight heterologous genes originated from different plants

[170]

 Resveratrol

Coumaroyl-CoA

Glucose

S. cerevisiae

0.415 g/L

~ 35

Fed-batch (fermenter, 1 L)

Inserting three heterologous genes originated from plant; Overexpressing genes encoding feedback resistant enzymes in SHK pathway and gene encoding post-translational deregulated acetyl-coA carboxylase; Multiple integration of pathway genes

[174]

Ethanol

0.531 g/L

~35

 Eriodictyol

Caffeoyl-CoA

Glucose

E. coli

0.054 g/L

Batch (shake-flask)

Overexpressing malonate carrier- and malonate synthase-coding genes involved in the malonate assimilation pathway; Repressing activity of two enzymes in fatty acid pathway by the addition of cerulenin; Introducing four heterologous genes

[159]