Metabolic engineering for the production of l-phenylalanine in Escherichia coli

Abstract

As one of the three proteinogenic aromatic amino acids, l-phenylalanine is widely applied in the food, chemical and pharmaceutical industries, especially in production of the low-calorie sweetener aspartame. Microbial production of l-phenylalanine has become attractive as it possesses the advantages of environmental friendliness, low cost, and feedstock renewability. With the progress of metabolic engineering, systems biology and synthetic biology, production of l-phenylalanine from glucose in Escherichia coli with relatively high titer has been achieved by improving the intracellular levels of precursors, alleviating transcriptional repression and feedback inhibition of key enzymes, increasing the export of l-phenylalanine, engineering of global regulators, and overexpression of rate-limiting enzymes. In this review, successful metabolic engineering strategies for increasing l-phenylalanine accumulation from glucose in E. coli are described. In addition, perspectives for further improvement of production of l-phenylalanine are discussed.

The De Novo Synthesis of 2-Phenylethanol from Glucose by the Synthetic Microbial Consortium Composed of Engineered Escherichia coli and Meyerozyma guilliermondii

“…Therefore, to increase the accumulation of l -Phe, tyrA was first knocked out by using CRISPR-Cas9 to prevent tyrosine synthesis and relieve its feedback inhibition on the expression of aroF (Figure A). In addition, the activities of 3-deoxy- d -arobino-heptulosonate 7-phosphate (DAHP) synthase including AroF , AroG , and AroH , and chorismate mutase–prephenate dehydrogenase (CM–PDT) encoded by pheA are two rate limiting steps for l -Phe synthesis, which is inhibited by the allosteric binding of l -Phe . Therefore, we further screened and obtained two antifeedback inhibitor genes of aroF and pheA from E.…”

Effects of Hydroxy-Alpha-Sanshool on Intestinal Metabolism in Insulin-Resistant Mice

“…An essential metabolic change associated with IR is amino acid metabolism, particularly BCAAs and aromatic amino acids (AAAs) [ 38 ]. L-phenylalanine (L-PHE), L-Tyrosine (L-Tyr), and L-tryptophan (L-TRP) are AAAs [ 39 ]. The two kinds of AAAs, tyrosine, and phenylalanine, are associated with diabetes risk [ 40 , 41 ].…”

Engineering of phenylalanine dehydrogenase from Thermoactinomyces intermedius for the production of a novel homoglutamate

“…In this work, we met with some challenges: first the genetically stable framework of the host micro-organism to grow at minimal growth conditions. To overcome this problem, we choose Escherichia coli as a model organism due to simple genetic manipulation, clear genetic background, and one of the prominent microorganisms used in metabolic engineering [ 41 ]. Its metabolism and regulation is well characterized and has a variety of genetic tools [ 42 ] like Keio knockout collection and MAGE [ 43 ], synthetic biology tools like promoters, well-characterized regulators and ribosome-binding sites [ 43 ], and systems biology tools like genome-scale models [ 44 ].…”