Engineering

Francisco Bolivar,Juan A Martínez,Guillermo Gosset,Alberto Rodriguez,Adelfo Escalante,Noemí Flores

doi:10.1186/preaccept-2032244031131285

Engineering

Francisco Bolivar, Juan A Martínez

Open Access

https://doi.org/10.1186/preaccept-2032244031131285

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Abstract

The production of aromatic amino acids using fermentation processes with recombinant microorganisms can be an advantageous approach to reach their global demands. In addition, a large array of compounds with alimentary and pharmaceutical applications can potentially be synthesized from intermediates of this metabolic pathway. However, contrary to other amino acids and primary metabolites, the artificial channelling of building blocks from central metabolism towards the aromatic amino acid pathway is complicated to achieve in an efficient manner. The length and complex regulation of this pathway have progressively called for the employment of more integral approaches, promoting the merge of complementary tools and techniques in order to surpass metabolic and regulatory bottlenecks. As a result, relevant insights on the subject have been obtained during the last years, especially with genetically modified strains of Escherichia coli. By combining metabolic engineering strategies with developments in synthetic biology, systems biology and bioprocess engineering, notable advances were achieved regarding the generation, characterization and optimization of E. coli strains for the overproduction of aromatic amino acids, some of their precursors and related compounds. In this paper we review and compare recent successful reports dealing with the modification of metabolic traits to attain these objectives.

Highlights

The aromatic amino acids (AAA), L-tryptophan (L-TRP), L-phenylalanine (L-PHE) and L-tyrosine (L-TYR), are the final products of the aromatic biosynthetic pathway comprising the shikimate (SHK) pathway, which connects central carbon metabolism (CCM) with the biosynthesis of chorismate (CHA), the last common precursor in the terminal branches for AAA biosynthesis (Figure 1) [1,2]
The AAA are essential components in the diet of higher animals and humans, they are used as dietary supplements and key precursors of industrial and pharmaceutical compounds
In this paper we review some notable advances in the generation, characterization and optimization of E. coli strains for the overproduction of AAA, some of their important precursors and related compounds

Summary

Introduction

The aromatic amino acids (AAA), L-tryptophan (L-TRP), L-phenylalanine (L-PHE) and L-tyrosine (L-TYR), are the final products of the aromatic biosynthetic pathway comprising the shikimate (SHK) pathway, which connects central carbon metabolism (CCM) with the biosynthesis of chorismate (CHA), the last common precursor in the terminal branches for AAA biosynthesis (Figure 1) [1,2]. The generation of synthetic parts in a faster, cheaper and more targeted way has enabled metabolic engineers to reach unprecedented biochemical diversity, exemplified by the production of plant compounds using precursors present in the aromatic biosynthetic pathway in E. coli In this way, combinations of simultaneous transcriptional modules and genetic platforms have resulted in strains with the ability to produce attractive compounds such as salvianic acid A [94], δ-tocotrienol and its intermediate 2-methyl-6-geranylgeranyl-benzoquinol [95,96] (Figure 2) and (S)-reticuline [97] (Figure 3). The same system was used to evaluate the capabilities for resveratrol production after

Conclusions

19. Gosset G

23. Gosset G

Findings

36. Liao JC