Natural 5-Aminolevulinic Acid: Sources, Biosynthesis, Detection and Applications

Abstract

5-Aminolevulinic acid (5-ALA) is the key precursor for the biosynthesis of tetrapyrrole compounds, with wide applications in medicine, agriculture and other burgeoning fields. Because of its potential applications and disadvantages of chemical synthesis, alternative biotechnological methods have drawn increasing attention. In this review, the recent progress in biosynthetic pathways and regulatory mechanisms of 5-ALA synthesis in biological hosts are summarized. The research progress on 5-ALA biosynthesis via the C4/C5 pathway in microbial cells is emphasized, and the corresponding biotechnological design strategies are highlighted and discussed in detail. In addition, the detection methods and applications of 5-ALA are also reviewed. Finally, perspectives on potential strategies for improving the biosynthesis of 5-ALA and understanding the related mechanisms to further promote its industrial application are conceived and proposed.

Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid

“…Two 5-ALA biosynthetic pathways, the C4 pathway (condensation of succinyl-coenzyme A and glycine) and C5 pathway (cascade reactions with glutamate as the precursor), have been discovered and characterized [5]. Since then, synthetic strains based on genetically tractable and well-studied platform microbes, mainly Escherichia coli and Corynebacterium glutamicum, have been engineered for microbial production of 5-ALA from renewable resources [6,7].…”

Impact of broad-spectrum antibiotics on the gut–microbiota–spleen–brain axis

“…We found that plasma levels of 5-ALA were significantly elevated in the ABX-treated mice, and negatively correlated with splenic neutrophils, macrophages, and spleen weight. Given the beneficial role of 5-ALA ( Jiang et al, 2022 ), the increase in 5-ALA levels induced by ABX treatment may have a compensatory effect on impaired splenic functions. Taken together, our findings suggest that ABX-induced microbiome depletion could affect the synthesis and metabolism of a number of host metabolites that regulate splenic cell populations and spleen function via humoral circulation.…”

A Non-functional γ-Aminobutyric Acid Shunt Pathway in Cyanobacterium Synechocystis sp. PCC 6803 Enhances δ-Aminolevulinic Acid Accumulation under Modified Nutrient Conditions

“…Amongst the numerous non-protein amino acids found in prokaryotic and eukaryotic living systems, δ-aminolevulinic acid (ALA) is considered particularly important due to its ubiquitous presence and multifunctional properties in the metabolism of bacteria, algae, plants and animals, as well as due to its use in cosmetic, agricultural and pharmaceutical industry products [ 4 ]. ALA is considered a significant intermediate in tetrapyrrole biosynthesis; it plays a critical role in respiration and photosynthesis by controlling chlorophyll metabolism in green organisms [ 5 ].…”

“…The biosynthesis of ALA inside the cells chiefly occurs via two distinct metabolic routes: the C4 pathway (Shemin pathway) and the C5 pathway (Beale pathway), as illustrated in Figure 1 . The C4 pathway appears in mammalian, fungal, protozoan and bacterial cells, in which ALA forms from succinyl-CoA and glycine via a single-step catalytic action of ALA synthase (ALAS) [ 5 ]. In the C5 pathway (hereafter referred to as the ‘ALA pathway’), occurring in blue-green algae (cyanobacteria), plants and several bacterial species, ALA forms from glutamate in three irreversible steps and is catalysed consecutively by the action of glutamyl-tRNA synthetase (GluRS), glutamyl-tRNA reductase (GluTR) and glutamate-1-semialdehyde 2,1-aminomutase (GSA-AM) [ 6 ].…”