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

Daniel J. Wichelecki, Jean Alyxa Ferolin Vendiola, Amy M. Jones, Nawar Al-Obaidi, Steven C. Almo, John A. Gerlt

Research output: Contribution to journalArticle

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 = 103-104 M-1 s-1) for dehydration of d-mannonate, low-efficiency (kcat/KM = 10-102 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.

Original languageEnglish (US)
Pages (from-to)5692-5699
Number of pages8
JournalBiochemistry
Volume53
Issue number35
DOIs
StatePublished - Sep 9 2014

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ASJC Scopus subject areas

  • Biochemistry

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