Relationships amongst some bacterial and yeast lactate and mandelate dehydrogenases

Fewson, Charles A.; Baker, Darren P.; Chalmers, Ronald; Keen, Jeffrey N.; Hamilton, Ian J; Scott, Alan; Yasin, Muhammad

doi:10.1099/00221287-139-6-1345

Cited by 11 publications

(5 citation statements)

References 32 publications

(42 reference statements)

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“…and Haemophilus influenzae (H.i.). The SNHGGRQ sequence conserved among flavin mononucleotide-containing ␣-hydroxy acid dehydrogenases and oxidases (7,11,20) is indicated by bold type. In the consensus sequence, a capital letter indicates that the amino acid predicted at that position was the same for all three genes, a lowercase letter indicates an amino acid common to two of the gene sequences, and a period indicates that all three genes had different amino acids at that position.…”

Section: Resultsmentioning

confidence: 99%

Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation

Erwin

Gotschlich

1996

J Bacteriol

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We report the cloning of lldA, a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH). Escherichia coli contains a single L-LDH gene (lldD) in the lld operon (previously lct). E. coli grown in complex media does not have L-LDH activity, but the activity is induced by growth in defined medium with L-lactate as the carbon source. In contrast, meningococci contain at least one L-LDH in addition to the lldA gene product. These enzymes are active in meningococci grown in complex media and are not dependent on growth in L-lactate. The predicted amino acid sequence of lldA is homologous to that of E. coli lldD and of other prokaryotic and eukaryotic flavin mononucleotide-containing enzymes that catalyze the oxidation of L-lactate and other small ␣-hydroxy acids. A mutant with a deletion in lldA was found to have reduced L-LDH activity. However, this mutant was able to grow on L-lactate, indicating that a second L-LDH must exist. Activity of the lldA enzyme was affected by growth conditions, being increased by growth on a defined medium with either L-lactate or pyruvate as the carbon source. For meningococci grown on a complex medium, activity of the lldA enzyme was increased by growth on plates or in well-aerated broth. A second L-lactate-oxidizing activity was seen in bacteria grown in poorly aerated broth. Neisseria gonorrhoeae contains a homolog of lldA. As for meningococci, mutation of the gonococcal lldA reduced L-LDH activity but did not affect growth on L-lactate.Neisseria meningitidis is able to grow well with either Dlactate or L-lactate as its principal carbon source (9). The D isomer of lactate is not produced by mammalian cells, but since it is produced from glucose by some lactic acid bacteria, it may be available to meningococci in the nasopharynx, the site of initial colonization. Lactate produced by the mammalian host is the L isomer and may be utilized by meningococci in the bloodstream or cerebrospinal fluid as well as in the nasopharynx. Study of the lactate-oxidizing enzymes and their regulation may provide insight into the physiology of meningococci at different stages of infection and the process of adaptation to various sites within the host.Several lactate-oxidizing enzymes of gram-negative bacteria have been characterized and shown to be membrane-associated flavoproteins that are components of the electron transport chain (18,19). The activity of these enzymes can be measured in intact bacteria and in some membrane fractions by lactate-dependent oxygen uptake or by lactate-dependent dye reduction. In general, these enzymes are isomer specific. However, in both Escherichia coli (29) and N. meningitidis (9), purified D-lactate dehydrogenase (D-LDH) has been found to have a low-affinity activity toward L-lactate in addition to a high-affinity D-lactate-oxidizing activity. We have previously described the purification of meningococcal D-LDH and the cloning of its gene, dld (9). Insertional inactivation of dld produced a mutant lacking D-LDH activity and unable to grow on D-lactate but wi...

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Section: Resultsmentioning

confidence: 99%

Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation

Erwin

Gotschlich

1996

J Bacteriol

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“…D-Mandelate dehydrogenases were found in Enterococcus faecalis [9], in Lactobacillus curvatus [lo] and in the yeast Rhodotorula graminis [11]. This latter enzyme was recently characterised and it was reported that no similarity could be found with any enzyme reported in the data bases over the known 30% of its sequence [12]. L. casei D-2-hydroxyisocaproate dehydrogenase (D-HOHxoDH) was also characterised [13] and the corresponding gene cloned in 1989 [14].…”

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confidence: 99%

“…Curiously, the latter enzyme [9, 101 readily reduces 2-oxoisocaproate but prefers benzoylformate (phenyl substitution on C3) which is not accepted by the former [2] which, however, readily reduces phenylpyruvate (phenyl substitution on C4). The binding pockets of these two enzymes must be quite different and this probably explains why their sequences seem to bear no resemblance [12].…”

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confidence: 99%

NAD⁺‐Dependent d‐2‐Hydroxyisocaproate Dehydrogenase of Lactobacillus Delbrueckii subsp. Bulgaricus

Bernard

Johnsen

Ferain

et al. 1994

European Journal of Biochemistry

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A genomic library from Lactobacillus delbrueckii subsp. bulgaricus was used to complement an Escherichia coli mutant strain deficient for both lactate dehydrogenase and pyruvate formate lyase, and thus unable to grow anaerobically. One recombinant clone was found to display a broad specificity NAD+-dependent D-2-hydroxyacid dehydrogenase activity. The corresponding gene (named hdhD) was subcloned and sequenced. The deduced amino acid sequence of the encoded enzyme indicates a 333-residue protein closely related to D-2-hydroxyisocaproate (i.e. 2-hydroxy-4-methyl-pentanoate) dehydrogenase (D-HO-HxoDH) of Lactobacillus casei and other NAD+-dependent D-lactate dehydrogenases (D-LDH) from several other bacterial species. The hdhD gene was overexpressed under the control of the lambda phage P, promoter and the enzyme was purified with a two-step method. The L. delbrueckii subsp. bulgaricus enzyme, like that of L. casei, was shown to be active on a wide variety of 2-oxoacid substrates except those having a branched P-carbon.NAD+-dependent 2-hydroxyacid dehydrogenases of broad substrate specificity have been reported in many species [l]. They catalyse the stereospecific and reversible reduction of various aliphatic and aromatic 2-oxocarboxylic acids to the corresponding 2-hydroxycarboxylic acids. The optically active products are not only valuable compounds as synthons for industrial processes as, for instance, in the production of semisynthetic antibiotics or pharmaceuticals [2], but they can also be used for clinical analysis of blood samples [3]. These enzymes can be divided into two groups on the basis of their substrate preference: mandelate dehydrogenase (or benzoylformate reductase), on the one hand, and 2-hydroxyisocaproate (i.e. 2-hydroxy-4-methylpentanoate) dehydrogenase (or 2-oxoisocaproate reductase), on the other hand. Each class can be further subdivided according to the D-or L-stereoisomer produced. Their actual substrate and function in vivo are not known.Lactobacillus confusus NAD'-dependent L-2-hydroxyisocaproate dehydrogenase (L-HO-HxoDH) was described for the first time in 1984 [4] and the corresponding gene was

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“…On the other hand, certain Lactobacilli are known to have D-2-hydroxyisocaproate dehydrogenases (D-HicDHs), which utilize still larger aliphatic or aromatic substrates than D-LDHs (7,16,18,22), although their actual physiological role is uncertain. Furthermore, the enzymes purified from Lactobacillus curvatus (17), Enterococcus faecalis (30), and the yeast Rhodotorula graminis (2,3,5,12) have been reported to efficiently catalyze the conversion between benzoylformic acid (C 6 H 5 -CO-COO Ϫ ) and D-mandelic acid (C 6 H 5 -CHOH-COO Ϫ ) and are called D-mandelate dehydrogenases (D-ManDHs) (17), although their crucial relationship to D-LDH remains uncertain (5,12). D-LDH-related enzymes such as D-HicDHs and D-ManDHs are promising for industrial application, because optically active 2-hydroxyacids are valuable for the synthesis of useful compounds (16)(17)(18)30).…”

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Two Forms of NAD-Dependent d -Mandelate Dehydrogenase in Enterococcus faecalis IAM 10071

Tamura

Ohkubo

Iwai

et al. 2002

Appl Environ Microbiol

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Two forms of NAD-dependent d-mandelate dehydrogenase (d-ManDHs) were purified from Enterococcus faecalis IAM 10071. While these two enzymes consistently exhibited high activity toward large 2-ketoacid substrates that were branched at the C3 or C4 position, they gave distinctly different Km and V max values for these substrates and had distinct molecular weights by gel electrophoresis and gel filtration.

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Relationships amongst some bacterial and yeast lactate and mandelate dehydrogenases

Cited by 11 publications

References 32 publications

Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation

Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation

NAD⁺‐Dependent d‐2‐Hydroxyisocaproate Dehydrogenase of Lactobacillus Delbrueckii subsp. Bulgaricus

Two Forms of NAD-Dependent d -Mandelate Dehydrogenase in Enterococcus faecalis IAM 10071

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Relationships amongst some bacterial and yeast lactate and mandelate dehydrogenases

Cited by 11 publications

References 32 publications

Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation

Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation

NAD+‐Dependent d‐2‐Hydroxyisocaproate Dehydrogenase of Lactobacillus Delbrueckii subsp. Bulgaricus

Two Forms of NAD-Dependent d -Mandelate Dehydrogenase in Enterococcus faecalis IAM 10071

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NAD⁺‐Dependent d‐2‐Hydroxyisocaproate Dehydrogenase of Lactobacillus Delbrueckii subsp. Bulgaricus