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Production of Cinnamic and p-Hydroxycinnamic Acids in Engineered Microbes.

Vargas-Tah A, Gosset G - Front Bioeng Biotechnol (2015)

Bottom Line: These strategies include the expression of feedback insensitive mutant versions of enzymes from the aromatic pathways, as well as genetic modifications to central carbon metabolism to increase biosynthetic availability of precursors phosphoenolpyruvate and erythrose-4-phosphate.These efforts have been complemented with strain optimization for the utilization of raw material, including various simple carbon sources, as well as sugar polymers and sugar mixtures derived from plant biomass.A systems biology approach to production strains characterization has been limited so far and should yield important data for future strain improvement.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México , Cuernavaca , Mexico.

ABSTRACT
The aromatic compounds cinnamic and p-hydroxycinnamic acids (pHCAs) are phenylpropanoids having applications as precursors for the synthesis of thermoplastics, flavoring, cosmetic, and health products. These two aromatic acids can be obtained by chemical synthesis or extraction from plant tissues. However, both manufacturing processes have shortcomings, such as the generation of toxic subproducts or a low concentration in plant material. Alternative production methods are being developed to enable the biotechnological production of cinnamic and (pHCAs) by genetically engineering various microbial hosts, including Escherichia coli, Saccharomyces cerevisiae, Pseudomonas putida, and Streptomyces lividans. The natural capacity to synthesize these aromatic acids is not existent in these microbial species. Therefore, genetic modification have been performed that include the heterologous expression of genes encoding phenylalanine ammonia-lyase and tyrosine ammonia-lyase activities, which catalyze the conversion of l-phenylalanine (l-Phe) and l-tyrosine (l-Tyr) to cinnamic acid and (pHCA), respectively. Additional host modifications include the metabolic engineering to increase carbon flow from central metabolism to the l-Phe or l-Tyr biosynthetic pathways. These strategies include the expression of feedback insensitive mutant versions of enzymes from the aromatic pathways, as well as genetic modifications to central carbon metabolism to increase biosynthetic availability of precursors phosphoenolpyruvate and erythrose-4-phosphate. These efforts have been complemented with strain optimization for the utilization of raw material, including various simple carbon sources, as well as sugar polymers and sugar mixtures derived from plant biomass. A systems biology approach to production strains characterization has been limited so far and should yield important data for future strain improvement.

No MeSH data available.


Related in: MedlinePlus

Central metabolism, aromatics biosynthetic pathways, and transport pathways from engineered E. coli. Dashed arrows indicate multiple enzyme reactions. EI, PTS enzyme I; HPr, PTS phosphohistidine carrier protein; EIIA, PTS glucose-specific enzyme II; PTS IICBGlc, integral membrane glucose permease; GalP, galactose permease; XylFGH, xylose transport proteins, AraFGH, arabinose transport proteins; DAHPS, DAHP synthase; aroGfbr, gene encoding a feedback-inhibition-resistant version of DAHPS; tktA, transketolase; tyrB, tyrosine aminotransferase gene; PAL, phenylalanine ammonia lyase; TAL, tyrosine ammonia lyase; C4H, cinnamate 4-hydroxylase; AaeXAB, efflux pump from E. coli; SprABC, efflux pump from P. putida; G6P, glucose-6-phosphate; F6P, fructose-6-phosphate; G3P, glyceraldehyde-3-phosphate; PEP, phosphoenolpyruvate; R5P, ribose-5-phosphate; Ru5P, ribulose-5-phosphate; S7P, sedoheptulose-7-phosphate; X5P, xylulose-5-phosphate; PYR, pyruvate; AcCoA, acetyl-CoA; TCA, tricarboxylic acids.
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Figure 1: Central metabolism, aromatics biosynthetic pathways, and transport pathways from engineered E. coli. Dashed arrows indicate multiple enzyme reactions. EI, PTS enzyme I; HPr, PTS phosphohistidine carrier protein; EIIA, PTS glucose-specific enzyme II; PTS IICBGlc, integral membrane glucose permease; GalP, galactose permease; XylFGH, xylose transport proteins, AraFGH, arabinose transport proteins; DAHPS, DAHP synthase; aroGfbr, gene encoding a feedback-inhibition-resistant version of DAHPS; tktA, transketolase; tyrB, tyrosine aminotransferase gene; PAL, phenylalanine ammonia lyase; TAL, tyrosine ammonia lyase; C4H, cinnamate 4-hydroxylase; AaeXAB, efflux pump from E. coli; SprABC, efflux pump from P. putida; G6P, glucose-6-phosphate; F6P, fructose-6-phosphate; G3P, glyceraldehyde-3-phosphate; PEP, phosphoenolpyruvate; R5P, ribose-5-phosphate; Ru5P, ribulose-5-phosphate; S7P, sedoheptulose-7-phosphate; X5P, xylulose-5-phosphate; PYR, pyruvate; AcCoA, acetyl-CoA; TCA, tricarboxylic acids.

Mentions: Bacteria and plants have the natural capacity for synthesizing a large number of aromatic compounds from simple carbon sources. The shikimate or common aromatic pathway is the main central metabolic branch leading to several biosynthetic pathways that produce various aromatic metabolites (Figure 1). The aromatic amino acids l-phenylalanine (l-Phe), l-tyrosine (l-Tyr), and l-tryptophan (l-Trp) are primary metabolites synthesized from simple carbon sources by plants and bacteria. Secondary metabolites, such as phenylpropanoids, are derived from l-Phe and l-Tyr and are produced mainly by plants. The phenylpropanoid acids cinnamic acid (CA) and p-hydroxycinnamic acid (pHCA), also known as coumaric acid, are two metabolites having nutraceutical and pharmaceutical properties (Chemler and Koffas, 2008). They also have applications as precursors of chemical compounds and materials, such as high-performance thermoplastics (Kaneko et al., 2006; Sariaslani, 2007).


Production of Cinnamic and p-Hydroxycinnamic Acids in Engineered Microbes.

Vargas-Tah A, Gosset G - Front Bioeng Biotechnol (2015)

Central metabolism, aromatics biosynthetic pathways, and transport pathways from engineered E. coli. Dashed arrows indicate multiple enzyme reactions. EI, PTS enzyme I; HPr, PTS phosphohistidine carrier protein; EIIA, PTS glucose-specific enzyme II; PTS IICBGlc, integral membrane glucose permease; GalP, galactose permease; XylFGH, xylose transport proteins, AraFGH, arabinose transport proteins; DAHPS, DAHP synthase; aroGfbr, gene encoding a feedback-inhibition-resistant version of DAHPS; tktA, transketolase; tyrB, tyrosine aminotransferase gene; PAL, phenylalanine ammonia lyase; TAL, tyrosine ammonia lyase; C4H, cinnamate 4-hydroxylase; AaeXAB, efflux pump from E. coli; SprABC, efflux pump from P. putida; G6P, glucose-6-phosphate; F6P, fructose-6-phosphate; G3P, glyceraldehyde-3-phosphate; PEP, phosphoenolpyruvate; R5P, ribose-5-phosphate; Ru5P, ribulose-5-phosphate; S7P, sedoheptulose-7-phosphate; X5P, xylulose-5-phosphate; PYR, pyruvate; AcCoA, acetyl-CoA; TCA, tricarboxylic acids.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4542537&req=5

Figure 1: Central metabolism, aromatics biosynthetic pathways, and transport pathways from engineered E. coli. Dashed arrows indicate multiple enzyme reactions. EI, PTS enzyme I; HPr, PTS phosphohistidine carrier protein; EIIA, PTS glucose-specific enzyme II; PTS IICBGlc, integral membrane glucose permease; GalP, galactose permease; XylFGH, xylose transport proteins, AraFGH, arabinose transport proteins; DAHPS, DAHP synthase; aroGfbr, gene encoding a feedback-inhibition-resistant version of DAHPS; tktA, transketolase; tyrB, tyrosine aminotransferase gene; PAL, phenylalanine ammonia lyase; TAL, tyrosine ammonia lyase; C4H, cinnamate 4-hydroxylase; AaeXAB, efflux pump from E. coli; SprABC, efflux pump from P. putida; G6P, glucose-6-phosphate; F6P, fructose-6-phosphate; G3P, glyceraldehyde-3-phosphate; PEP, phosphoenolpyruvate; R5P, ribose-5-phosphate; Ru5P, ribulose-5-phosphate; S7P, sedoheptulose-7-phosphate; X5P, xylulose-5-phosphate; PYR, pyruvate; AcCoA, acetyl-CoA; TCA, tricarboxylic acids.
Mentions: Bacteria and plants have the natural capacity for synthesizing a large number of aromatic compounds from simple carbon sources. The shikimate or common aromatic pathway is the main central metabolic branch leading to several biosynthetic pathways that produce various aromatic metabolites (Figure 1). The aromatic amino acids l-phenylalanine (l-Phe), l-tyrosine (l-Tyr), and l-tryptophan (l-Trp) are primary metabolites synthesized from simple carbon sources by plants and bacteria. Secondary metabolites, such as phenylpropanoids, are derived from l-Phe and l-Tyr and are produced mainly by plants. The phenylpropanoid acids cinnamic acid (CA) and p-hydroxycinnamic acid (pHCA), also known as coumaric acid, are two metabolites having nutraceutical and pharmaceutical properties (Chemler and Koffas, 2008). They also have applications as precursors of chemical compounds and materials, such as high-performance thermoplastics (Kaneko et al., 2006; Sariaslani, 2007).

Bottom Line: These strategies include the expression of feedback insensitive mutant versions of enzymes from the aromatic pathways, as well as genetic modifications to central carbon metabolism to increase biosynthetic availability of precursors phosphoenolpyruvate and erythrose-4-phosphate.These efforts have been complemented with strain optimization for the utilization of raw material, including various simple carbon sources, as well as sugar polymers and sugar mixtures derived from plant biomass.A systems biology approach to production strains characterization has been limited so far and should yield important data for future strain improvement.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México , Cuernavaca , Mexico.

ABSTRACT
The aromatic compounds cinnamic and p-hydroxycinnamic acids (pHCAs) are phenylpropanoids having applications as precursors for the synthesis of thermoplastics, flavoring, cosmetic, and health products. These two aromatic acids can be obtained by chemical synthesis or extraction from plant tissues. However, both manufacturing processes have shortcomings, such as the generation of toxic subproducts or a low concentration in plant material. Alternative production methods are being developed to enable the biotechnological production of cinnamic and (pHCAs) by genetically engineering various microbial hosts, including Escherichia coli, Saccharomyces cerevisiae, Pseudomonas putida, and Streptomyces lividans. The natural capacity to synthesize these aromatic acids is not existent in these microbial species. Therefore, genetic modification have been performed that include the heterologous expression of genes encoding phenylalanine ammonia-lyase and tyrosine ammonia-lyase activities, which catalyze the conversion of l-phenylalanine (l-Phe) and l-tyrosine (l-Tyr) to cinnamic acid and (pHCA), respectively. Additional host modifications include the metabolic engineering to increase carbon flow from central metabolism to the l-Phe or l-Tyr biosynthetic pathways. These strategies include the expression of feedback insensitive mutant versions of enzymes from the aromatic pathways, as well as genetic modifications to central carbon metabolism to increase biosynthetic availability of precursors phosphoenolpyruvate and erythrose-4-phosphate. These efforts have been complemented with strain optimization for the utilization of raw material, including various simple carbon sources, as well as sugar polymers and sugar mixtures derived from plant biomass. A systems biology approach to production strains characterization has been limited so far and should yield important data for future strain improvement.

No MeSH data available.


Related in: MedlinePlus