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.
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Authors | Daniel J Wichelecki, Jean Alyxa Ferolin Vendiola, Amy M Jones, Nawar Al-Obaidi, Steven C Almo, John A Gerlt |
Journal | Biochemistry
(Biochemistry)
Vol. 53
Issue 35
Pg. 5692-9
(Sep 09 2014)
ISSN: 1520-4995 [Electronic] United States |
PMID | 25145794
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Bacterial Proteins
- Escherichia coli Proteins
- Sugar Acids
- idonic acid
- gulonic acid
- Hydro-Lyases
- gluconate dehydratase
- mannonate dehydratase
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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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