De novo β-alanine synthesis in α-proteobacteria involves a β-alanine synthase from the uracil degradation pathway

Abstract

{beta}-alanine synthesis in bacteria occurs by the decarboxylation of L-aspartate as part of the pantothenate synthesis pathway. In the other two domains of life we find different pathways for {beta}-alanine formation, such as sources from spermine in plants, uracil in yeast and by transamination reactions in insects and mammals. There are also promiscuous decarboxylases that can decarboxylate aspartate. Several bioinformatics studies about the conservation of pantothenate synthesis pathway performed on bacteria, archaea and eukaryotes, have shown a partial conservation of the pathway. As a part of our work, we performed an analysis of the prevalence of reported {beta}-alanine synthesis pathways in 204 genomes of alpha-proteobacteria, with a focus on the Rhizobiales order. The aim of this work was to determine the enzyme or pathway used to synthetize {beta}-alanine in Rhizobium etli CFN42. Our bioinformatics analysis showed that this strain encodes the pyrimidine degradation pathway in its genome. We obtained a {beta}-alanine synthase (amaB) mutant that was a {beta}-alanine auxotroph. Complementation with the cloned gene restored the wild type phenotype. Biochemical analysis confirmed that the recombinant AmaB catalyzed the formation of {beta}-alanine from 3-Ureidopropionic acid in vitro. Here we show a different way in bacteria to produce this essential metabolite.\n\nImportanceSince the pioneer studies of Cronan (1980) on {beta}-alanine synthesis in E. coli, it has been assumed that the decarboxilation of aspartate by the L-aspartate--decarboxylase its the main enzymatic reaction for {beta}-alanine synthesis in bacteria. Forty years later, while we were studying the pantothenic acid synthesis in rhizobia, we demonstrate that a numerous and diverse group of bacteria classified as -proteobacteria synthesize {beta}-alanine de novo using {beta}-alanine synthase, the last enzyme from the reductive pathway for uracil degradation.\n\nAdditionally, there is a growing interest in {beta}-amino acid due to its remarkable pharmaceuticals properties as hypoglycemic, antiketogenic and anti-fungal agents.