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Table 1 The systems metabolic engineering strategies on shikimate pathway for the microbial production of aromatic compounds

From: Metabolic engineering of microorganisms for production of aromatic compounds

Host

Product

Precursor

Carbon source

Titer

Time (h)

Bioprocess strategy

Systems metabolic engineering strategies

References

E. coli

PHBA

CHR

Glucose

12 g/L

72

Fed-batch (fermenter)

Overexpressing ubiC and particular genes in PP and SHK pathway

[25]

cis, cis-Muconic acid

DHS

Glucose

36.8 g/L

48

Fed-batch (fermenter, 2 L)

Inserting three heterologous genes from different microorganisms, being responsible for the product synthesis, deleting SDH-coding gene

[38]

AA

Glycerol/glucose

0.389 g/L

32

Batch (shake flask)

Optimizing AA pathway through overexpressing genes in PP and SHK pathway and shunting tryptophan biosynthesis; screening target genes being responsible for the biosynthesis from AA

[40]

2,3-DHBA

Glycerol/glucose

0.480 g/L

48

Batch (shake flask)

Screening and characterization of new BDC enzyme from different organisms; overexpressing target genes; deleting gene responsible for degradation of 2,3-DHBA

[41]

4HBA

Glucose

0.170 g/L

24

Batch (shake flask)

Integrating heterologous genes for the synthesis of CMA from precursor 4HBA to target product; over- and co-expressing native target genes and mutated ones; deleting genes in PEP–PTS

[42]

SA

Glycerol/glucose

1.5 g/L

48

Batch (shake flask)

Shunting SHK pathway from chorismate to aromatic amino acids; overexpressing genes in CCM and SHK pathway; Integrating heterologous genes being responsible in SA anabolism and catabolism

[43]

Salicylic acid

CHA

Glycerol/glucose

1.2 g/L

48

Batch (shake flask)

CHA

Glucose

11.5 g/L

48

Batch (fermenter, 2 L)

Replacing endogenous PTS system; Deleting genes of enzyme converting PEP to PYR; Integrating genes catalyzing product formation via CHR

[64]

PABA

CHA

Glucose

4.8 g/L

48

Fed-batch (shake flask)

Overexpressing feedback resistance gene at entrance of SHK pathway and heterologous genes; the integration of fused type ADC synthase

[70]

Gallic acid

DHS

Glucose

20 g/L

48

Fed-batch (fermenter)

Discovering side activity of pobA mutant to produce gallic acid from protocatechuic acid.

[73]

Pyrogallol

2,3-DHBA

2,3-DHBA

0.893 g/L

24

Fed-batch (shake-flask)

Identifying and characterizing 2,3-DHBA MNX1 from different sources; Integrating nahG-encoded MNX1; Optimizing CCM and SHK pathway with EntCBA activity

[74]

1.04 g/L

Autoxidation with oxygen scavenging agent ascorbic acid into the medium

Gallic acid

PHBA

Glucose/glycerol

1.266 g/L

36

Batch (shake-flask)

Mutating pobA (Y385F/T294A) from Pseudomonas aeruginosa; step-wise upstream pathway engineering with overexpression of UbiC to increase carbon flux to precursor

[75]

Quinic acid

DHQ

Glucose

4.8 g/L

N.A

Batch (shake-flask)

Integration of gene encoding quinic acid dehydrogenase in Klebsiella pneumaniae

[76]

Glucose

49 g/L

48

Fed-batch (fermenter, 2 L)

Integration of aroE encoded shikimate dehydrogenase

[77]

PDC

DHS

Glucose

16.72 g/L

60

Fed-batch (fermenter, 6.6 L)

Overexpressing feedback resistant variant aroG, ppsA and shiA; Integrating three heterologous genes

[39]

C. glutamicum

PHBA

CHA

Glucose

36.6 g/L

24

Growth arrested bioprocess (fermenter, 1 L)

Deleting target genes in competing pathway in CCM and SHK pathway; Screening and introducing best ubiC-encoded enzyme; Stepwise overexpressing the genes in PP and SHK pathway

[26]

PABA

CHA

Glucose

43 g/L

48

Fed-batch (fermenter, 1 L)

Screening pab genes from different microorganisms for target synthesis; Introducing fused ADC synthase from C. callunae and ADC4 lyase from X. bovienii

[71]

P. putida

cis, cis-Muconic acid

DHS

Glucose

4.92 g/L

54

Fed-batch (fermenter, 0.5 L)

Co-expression of two-genetically associated protein with PCA decarboxylase

[46]

S. cerevisiae

PHBA

CHA

Glucose

0.089 g/L

> 150

Pulse-feeding (fermenter, 1 L)

Deleting target genes for alleviated negative feedback; integration and overexpression of chorismate lyase originated from E. coli

[28]

Glucose

0.148 g/L

N.A

Batch (shake flask)

Quorum sensing linked RNA interference for separate growth and production phase

[29]

cis, cis-Muconic acid

DHS

Glucose

1.56 mg/L

170

Batch (shake flask)

Screening and combining best candidates of heterologous genes s catalyzing the reactions from DHS to cis–cis muconic acid

[44]

Glucose

141 mg/L

108

Batch (shake flask)

Screening and combining target genes and their putative concerned with targeted product; overexpressing PP pathway specific gene and feedback resistant mutant gene in SHK pathway

[45]

PABA

CHA

Glucose

0.034 g/L

> 150

Pulse-feeding (fermenter, 1 L)

Eliminating the genes on the entry towards aromatic amino acid pathway; overproducing gene related to product

[28]

Glucose

> 0.068 g/L

130

Batch (shake flask)

Screening additional allels of target homologous 2 genes being responsible for PABA production; combining them each other for their overexpression

[69]

Glycerol

0.215 g/L

Fed-batch (fermenter)