Engineering

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.

Advanced Biotechnology: Metabolically Engineered Cells for the Bio‐Based Production of Chemicals and Fuels, Materials, and Health‐Care Products

“…Further improvement can be expected from the current achievements in strain engineering 63b. 92b, 153 The collected expertise has additionally driven the production of related aromatic compounds, mainly with E. coli 91a. Shikimate, itself an intermediate of the aromatic amino acid metabolism, is probably the most popular and successful example thereof, with titers of 80 g L −1 achieved 25a.…”

Elucidation of the co-metabolism of glycerol and glucose in Escherichia coli by genetic engineering, transcription profiling, and 13C metabolic flux analysis

“…One metabolic engineering strategy to relax CCR is the inactivation of PTS genes [13, 17, 18]. The part PEP not consumed in glucose transport was canalized to shikimate pathway [17], which is a very important route for the synthesis of aromatic amino acids and natural products [19]. Therefore, we constructed a CCR-negative Δ ptsGglpK* mutant by both blocking a key glucose transporter gene ptsG and replacing the native glpK with glpK22 from E. coli Lin 43 to enhance the glycerol conversion [12].…”

Chromosome engineering of Escherichia coli for constitutive production of salvianic acid A

“…The biosynthetic pathway of l -tyrosine is tightly regulated by l -tyrosine feedback and transcription repression [34]. A variety of metabolic engineering approaches have been use to improve l -tyrosine production by deleting repressing gene tyrR and overexpressing feedback-resistant genes aroG fbr and tyrA fbr , and other genes of limited steps on plasmids [35, 36]. Plasmid-mediated l -tyrosine producer strains needed the addition of corresponding antibiotics and IPTG to control gene overexpression of interest [37–39].…”