Abstract
Pantothenate is an indispensable vitamin precursor of the synthesis of coenzyme A (CoA), a key metabolite required in over 100 metabolic reactions. β‐Alanine (β‐ala) is an indispensable component of pantothenate. Due to the metabolic relevance of this pathway, we assumed that orthologous genes for ß‐alanine synthesis would be present in the genomes of bacteria, archaea, and eukaryotes. However, comparative genomic studies revealed that orthologous gene replacement and loss of synteny occur at high frequency in panD genes. We have previously reported the atypical plasmid‐encoded location of the pantothenate pathway genes panC and panB (two copies) in R. etli CFN42. This study also revealed the unexpected absence of a panD gene encoding the aspartate decarboxylase enzyme (ADC), required for the synthesis of β‐ala. The aim of this study was to identify the source of β‐alanine in Rhizobium etli CFN42. In this study, we present a bioinformatic analysis and an experimental validation demonstrating that the source of β‐ala in this R. etli comes from β‐alanine synthase, the last enzyme of the uracil degradation pathway.
Highlights
Β-Alanine is a nonproteinogenic β-amino acid that occurs in all living organisms
Pioneer studies performed in E. coli and γ-proteobacteria defined that β-ala was synthesized by the decarboxylation of L-aspartate in a one-step reaction catalyzed by aspartate decarboxylase enzyme (ADC)
It has been assumed that the main source of β-ala in prokaryotes comes from the decarboxylation of aspartate in a single enzymatic step catalyzed by ADC
Summary
Β-ala is indispensable for the synthesis of pantothenate, the precursor of the essential cofactor coenzyme A (CoA). The major pathway for β-ala synthesis in Escherichia coli is the decarboxylation of aspartate by aspartate decarboxylase (ADC; Cronan, 1980). Since the majority of archaea lack homologues of the E. coli K12 acetyl-CoA synthesis pathway genes, the mechanism of pantothenate/CoA biosynthesis has not been completely deduced in these organisms. The pantothenate synthesis pathway, which includes a glutamate decarboxylase (GAD) that substitutes for ADC and uses pyridoxal 5'-phosphate (PLP) as a cofactor, was reported in archaea (Tomita, Yokooji, Ishibashi, Imanaka, & Atomia, 2014). Prokaryotes and eukaryotes have an indispensable requirement for β-ala for the synthesis of coenzyme A (CoA), the pathways involved in its synthesis are very diverse. The dihydropyrimidinase enzyme catalyzes the hydration of dihydrouracil to produce N-carbamoyl-β-ala, which is hydrolyzed to β-ala, CO2, and NH3, by β-ala synthase (Campbell, 1957)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
