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Investigating the physiological roles of low-efficiency D-mannonate and D-gluconate dehydratases in the enolase superfamily: pathways for the catabolism of L-gulonate and L-idonate.

Abstract
The sequence/function space in the D-mannonate dehydratase subgroup (ManD) of the enolase superfamily was investigated to determine how enzymatic function diverges as sequence identity decreases [Wichelecki, D. J., et al. (2014) Biochemistry 53, 2722-2731]. That study revealed that members of the ManD subgroup vary in substrate specificity and catalytic efficiency: high-efficiency (kcat/KM = 10(3)-10(4) M(-1) s(-1)) for dehydration of D-mannonate, low-efficiency (kcat/KM = 10-10(2) M(-1) s(-1)) for dehydration of D-mannonate and/or D-gluconate, and no activity. Characterization of high-efficiency members revealed that these are ManDs in the D-glucuronate catabolic pathway {analogues of UxuA [Wichelecki, D. J., et al. (2014) Biochemistry 53, 4087-4089]}. However, the genomes of organisms that encode low-efficiency members of the ManDs subgroup encode UxuAs; therefore, these must have divergent physiological functions. In this study, we investigated the physiological functions of three low-efficiency members of the ManD subgroup and identified a novel physiologically relevant pathway for L-gulonate catabolism in Chromohalobacter salexigens DSM3043 as well as cryptic pathways for L-gulonate catabolism in Escherichia coli CFT073 and L-idonate catabolism in Salmonella enterica subsp. enterica serovar Enteritidis str. P125109. However, we could not identify physiological roles for the low-efficiency members of the ManD subgroup, allowing the suggestion that these pathways may be either evolutionary relics or the starting points for new metabolic potential.
AuthorsDaniel J Wichelecki, Jean Alyxa Ferolin Vendiola, Amy M Jones, Nawar Al-Obaidi, Steven C Almo, John A Gerlt
JournalBiochemistry (Biochemistry) Vol. 53 Issue 35 Pg. 5692-9 (Sep 09 2014) ISSN: 1520-4995 [Electronic] United States
PMID25145794 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Sugar Acids
  • idonic acid
  • gulonic acid
  • Hydro-Lyases
  • gluconate dehydratase
  • mannonate dehydratase
Topics
  • Bacterial Proteins (genetics, metabolism)
  • Chromohalobacter (enzymology, genetics)
  • Escherichia coli Proteins (genetics, metabolism)
  • Gene Knockout Techniques
  • Halomonas (enzymology, genetics)
  • Hydro-Lyases (genetics, metabolism)
  • Kinetics
  • Metabolic Networks and Pathways
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Salmonella enteritidis (enzymology, genetics)
  • Substrate Specificity
  • Sugar Acids (metabolism)

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