From: Metabolic engineering of microorganisms for production of aromatic compounds
Product | Precursor | Carbon source | Host | Titer | Time (h) | Bioprocess strategy | Systems metabolic engineering strategies | References |
---|---|---|---|---|---|---|---|---|
Phenylpyruvate derivatives | ||||||||
 d-PHG | S-MA | Glucose | E. coli | 0.036 g/L | 24 | Batch (shake-flask) | Integrating genes encoding feedback resistant DAHP and bifunctional chorismate mutase/prephenete dehydratase; Deleting three genes in competing pathway using PPA and CHA; Construction 3-step artificial pathway from CHA to d-PHG | [84] |
 l-PHG | S-MA | Glucose | E. coli | – | 48 | Batch (shake-flask) | Screening better HpgT activity from different sources; Deleting genes in competing pathway using PPA; Construction 3-step artificial pathway from CHA to l-PHG | [86] |
 S-MA | PPA | Glucose | E. coli | 0.74 g/L | 24 | Batch (shake-flask) | Integrating genes encoding feedback resistant DAHP and bifunctional chorismate mutase/prephenete dehydratase; Their overexpression with S-MA; Deleting genes responsible for synthesis of l-TRP, l-TYR and l-PHE in competing pathways using CHA; Construction 3-step artificial pathway from CHA to R-MA | [87] |
 R-MA | S-MA | 1.02 g/L | 84 | |||||
 S-MA | PPA | Glucose | S. cerevisiae | 0.236 g/L | 120 | Batch (shake-flask) | Screening better HmaS activity from different microorganisms; Overexpressing genes (encoding pentafunctional protein and feedback two isozyme of resistant DAHP synthase); Deleting genes phenylpyruvate decarboxylase to reduce flux towards Ehrlich pathway | [88] |
 d-PHE | PPA | Glucose | E. coli | 1.72 g/L | 60 | Fed-batch (fermenter, 15 L) | Screening and homology based modeling of d-aminoacid transferase (Dat) from three Bacillus species; Constructing artificial d-PHE synthetic operon including each Dat gene | [89] |
 l-PhLA | PPA | Glucose | E. coli | 1.9 g/L | 24 | Batch (shake-flask) | Integration feedback-resistant allel of gene involved in SHK and l-PHE amino acid pathway; Deleting genes in competing pathway using CHA. Introducing lactate dehydrogenase with heterologous phenylpyruvate reductase | [91] |
 Poly-(3HB-co-d-PhLA) | PPA | Glucose | E. coli | 13.9 g/L | 96 | Fed-batch (fermenter, 6.6 L) | Identifying and introducing the gene encoding CoA transferase; integrating gene of enzyme responsible conversion from glucose to d-PhLA. Modulating flux under different promoters | [92] |
 Cinnamic acid | d-PhLA | Glucose | E. coli | 1.7 g/L | 30 (aerobic phase) | Batch coculture (shake-flask) | Integrating phenylpyruvate reductase-coding pprA from Wickerhamia fluorescens in d-PhLA producer strain; Integrating phenyllactate dehydratase-coding fldABCI from Clostridium sporogens in CA producer strain; Performing stepwise process; Optimizing cultivation time of aerobic phase followed by anaerobic one | [105] |
Phenylalanine derivatives | ||||||||
 Pinosylvin | Cinnamoyl-CoA | Glucose + CA | C. glutamicum | 0.121 g/L | 72 | Batch (shake-flask) | Deleting three gene cluster; Integrating 4CL and STS-coding genes from plant sources; Supplying cerulenin to inhibit activity of enzymes in fatty acid synthesis using malonyl-CoA | [116] |
Cinnamoyl-CoA | Glucose | E. coli | 0.281Â g/L | 48 | Batch (shake-flask) | Constructing two expression modules; Optimizing expression levels by combining promoter type and copy number in these expression modules; Designing upstream pathway module to direct carbon flux towards precursor; Designing downstream pathway module to produce the molecule of interest | [117] | |
 Chrysin | Pinocembrin | Galactose + acetate | S. cerevisiae | 0.001 g/L | 92 | Batch (shake-flask) | Introducing and overexpressing parsley FSI gene into biosynthetic pinocembrin pathway | [162] |
Galactose + raffinose | 0.002 g/L | 92 | Batch (shake-flask) | Introducing and overexpressing snapdragon gene (encoding flavone synthase II) and yeast gene (encoding P450 reductase) into biosynthetic pinocembrin pathway |  | |||
Pinocembrin | Glucose + l-PHE | E. coli | 0.0094 g/L | 36 | Batch (shake-flask) | Introducing FNS1 gene from Petroselinum crispum into biosynthetic pinocembrin metabolic pathway comprising PAL/TAL, 4CL, CHS, CHI and ACC (encoded by dtsR1 and accBC) | [164] | |
 Cinnamic acid | l-PHE | Glucose + casaminoacids | E. coli | 6.9 g/L | 86 | Fed-batch (fermenter, 2 L) | Screening appropriate promoter to express Streptomyces maritimus PAL gene; Investigating the effect of different supplements in feeding solution on pH-stat fed-batch fermentation | [106] |
Styrene | CA | Glucose | E. coli | 0.26Â g/L | 29 | Batch (shake-flask) | Introducing genes encoding plant phenylalanine ammonia lyase and yeast trans-cinnamate decarboxylase into l-PHE overproducer strain lacking multiple genes and expressing genes encoding feedback resistant enzymes in SHK pathway | [107] |
 Pinocembrin | Cinnamyl-CoA | Glucose | E. coli | 0.710 g/L | 36 | Batch (shake-flask) | Overexpressing malonate carrier- and malonate synthase-coding genes involved in the malonate assimilation pathway; Repressing activity of two genes in fatty acid pathway by the addition of cerulenin | [159] |
 Galangin | Pinocembrin | Glucose + l-PHE | E. coli | 0.001 g/L | 36 | Batch (shake-flask) | Introducing F3H and FLS gene from Citrus species into biosynthetic pinocembrin metabolic pathway comprising PAL/TAL, 4CL, CHS, CHI and ACC (encoded by dtsR1 and accBC) | [164] |