5-Aminolevulinic acid production: strategies for microbial biosynthesis, advances, and perspective

5-Aminolevulinic acid is an intermediate in the biosynthesis of tetrapyrrole, which is found in porphyrins, heme, and vitamin B12 and has various applications in agriculture, medicine, and cancer diagnostics. There are two different pathways in which 5-aminolevulinic acid can be produced: C4 pathway (Shemin pathway), which is present in purple bacteria, yeasts, and mammalian cells, and C5 pathway, which is present in many plants and some microorganisms. Today, 5-aminolevulinic acid is mostly produced by photosynthetic bacteria since the chemical synthesis of 5-aminolevulinic acid in comparison with microbial production has lower yields, and is more complicated by both numerous steps of synthesis and harmful coproducts. This article is devoted to the biosynthesis of 5-aminolevulinic acid by purple nonsulfur photosynthetic bacteria belonging to genera Rhodobacter, Rhodopseudomonas, and Rhodospirillum. Within the research, molecular-genetic identification and specification of the taxonomic position of the most active producing strains were carried out. Induced chemical mutagenesis was performed to increase the yield of 5-aminolevulinic acid in strain producers. The influence of various compounds in the compositions of nutrient media and that of environmental factors (temperature, illumination parameters, pH) on the growth and synthesis of 5-aminolevulinic acid in selected mutants of purple nonsulfur photosynthetic bacteria was revealed. A maximal yield of 5-aminolevulinic acid under laboratory and pilot-scale conditions was demonstrated. An economic efficiency of the synthesis of 5-aminolevulinic acid by a microbiological method was calculated.