The many roles of glutamate in metabolism

Abstract

The amino acid glutamate is a major metabolic hub in many organisms and as such is involved in diverse processes in addition to its role in protein synthesis. Nitrogen assimilation, nucleotide, amino acid, and cofactor biosynthesis, as well as secondary natural product formation all utilize glutamate in some manner. Glutamate also plays a role in the catabolism of certain amines. Understanding glutamate's role in these various processes can aid in genome mining for novel metabolic pathways or the engineering of pathways for bioremediation or chemical production of valuable compounds.

Keywords: Lanthipeptides; Lantibiotics; Natural products; Non-ribosomal peptide synthetase; Thiopeptides.

Fig. 1

Glutamate biosynthetic pathways. Glutamate is made from the citric acid cycle intermediate 2-oxoglutarate (2-OG) by reductive amination with either ammonium or glutamine as the nitrogen source

Fig. 2

Glutamate is the major nitrogen donor in metabolism. a Glutamate is the nitrogen donor, through glycine and aspartate, for about half of the nitrogens, indicated in red, in nucleotides. b Glutamate donates nitrogen for other amino acids through the action of glutamate transaminases. c Carbons in proline and arginine that come from glutamate are indicated by red circles

Fig. 3

Glutamate (shown in red) is used as a building block for the construction of more complex molecules

Fig. 4

Glutamate derived building blocks (shown in red) can be used during biosynthesis of complex natural products

Fig. 5

Glutamylation (shown in red) serves as a protecting group to prevent cyclization. a During putrescine catabolism, intermediates on the pathway are glutamylated to potentially prevent the spontaneous cyclization of the γ-aminobutyraldehyde to Δ¹-pyrroline. b During butirosin biosynthesis, glutamylation may block cyclization of aminobutyryl thioester intermediates to 5-membered lactams

Fig. 6

Glutamylation (shown in red) may block off-pathway N-oxidation. Intermediates during aniline (a) and isopropylamine (b) catabolism are glutamylated, which might prevent N-oxidation of the amine

Fig. 7

Glutamylated-tRNA is involved in biosynthetic pathways. a The biosynthesis of the tetrapyrrole precursor aminolevulinic acid proceeds through a Glu-tRNA^Glu intermediate. b Biosynthesis of the antimicrobial lanthipeptide nisin. c During biosynthesis of nisin, dehydrated amino acids are produced in a Glu-tRNA^Glu dependent manner