Is there methylmalonyl CoA mutase in Aspergillus nidulans?

Ledley, Fred D.; Crane, Ana M.; Klish, Kathryn T.; May, Gregory S.

doi:10.1016/0006-291x(91)90648-q

Cited by 17 publications

(17 citation statements)

References 12 publications

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“…Valine is likely catabolized to methylmalonate semialdehyde via an incomplete cycle of β‐ox (Bachhawat et al ., 1957; Robinson and Coon, 1957) and then converted to propionyl‐CoA and CO 2 (Sokatch et al ., 1968). A. nidulans lacks methylmalonyl‐CoA mutase, an enzyme of the mammalian valine catabolism pathway, as assessed biochemically (Ledley et al ., 1991) and by BLAST analysis, but contains a homologue of the bacterial propionyl‐CoA‐yielding methylmalonate semialdehyde dehydrogenase, locus AN3591.2. Despite the similarities in the β‐ox steps, the only common enzyme between the isoleucine, valine, and strain‐chain fatty acid pathways in mammals is the enoyl‐CoA hydratase (Robinson et al ., 1956; Bachhawat et al ., 1957; Ikeda et al ., 1983; Luo et al ., 1995).…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial β‐oxidation in Aspergillus nidulans

Maggio-Hall

Keller

2004

Molecular Microbiology

129

127

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Section: Resultsmentioning

confidence: 99%

Mitochondrial β‐oxidation in Aspergillus nidulans

Maggio-Hall

Keller

2004

Molecular Microbiology

129

127

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“…In contrast to fungi, humans metabolize propionylCoA exclusively via the coenzyme B 12-dependent methylmalonyl-CoA pathway, which is not present in fungi (Ledley et al, 1991). With the exception of propionyl-CoA, the methylmalonyl-CoA pathway possesses no common intermediates with that of the methylcitrate cycle, although disorders in propionyl-CoA metabolism lead to severe diseases like propionic or methylmalonic acidemia (Deodato et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis

et al. 2007

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SummaryInvasive aspergillosis is a life-threatening disease mainly caused by the fungus Aspergillus fumigatus. In immunocompromised individuals conidia are not efficiently inactivated, which can end in invasive fungal growth. However, the metabolic requirements of the fungus are hardly known. Earlier investigations revealed an accumulation of toxic propionyl-CoA in a methylcitrate synthase mutant, when grown on propionyl-CoA-generating carbon sources. During invasive growth propionyl-CoA could derive from proteins, which are released from infected host tissues. We therefore assumed that a methylcitrate synthase mutant might display an attenuated virulence. Here we show that the addition of propionate to cell culture medium enhanced the ability of alveolar macrophages to kill methylcitrate synthase mutant but not wild-type conidia. When tested in a murine infection model, the methylcitrate synthase mutant displayed attenuated virulence and, furthermore, was cleared from tissues when mice survived the first phase of acute infection. The amplification of cDNA from infected mouse lungs confirmed the transcription of the methylcitrate synthase gene during invasion, which leads to the suggestion that amino acids indeed serve as growth-supporting nutrients during invasive growth of A. fumigatus. Thus, blocking of methylcitrate synthase activity abrogates fungal growth and provides a suitable target for new antifungals.

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“…The recombinant MCM apoenzyme has been expressed at high levels in Saccharomyces cerevisiae for biochemical analysis and has been shown to exhibit kinetic parameters indistinguishable from the native enzyme (Andrews, E., R. Jansen, A. M. Crane, M. F. Wilkemeyer, D. McDonnell, and F. D. Ledley, unpublished data). Of particular relevance to the present experiments is the fact that S. cerevisiae does not have endogenous MCM (14) and does not produce adenosylcobalamin, so that the recombinant MCM produced in this organism is entirely apoenzyme.…”

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confidence: 98%

Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria.

Crane¹,

Jansen²,

Andrews³

et al. 1992

J. Clin. Invest.

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Distinct genotypic and phenotypic forms of methylmalonyl CoA mutase (MCM) apoenzyme deficiency can be delineated by biochemical analysis of mutant fibroblasts. One form, designated mut-, expresses a phenotype in which residual enzyme activity is evident in cultured cells exposed to high concentrations of hydroxycobalamin. We describe cloning of an MCM cDNA from cells exhibiting a mut-phenotype and characterization of the mutant gene product overexpressed in primary mut' human fibroblasts and Saccharomyces cerevisiae. Three novel base changes were observed. Recombinant clones containing one of these base changes (G717V) express four characteristics of the mut-phenotype: failure to constitute 14Cqpropionate incorporation activity in fibroblasts assayed under basal cell culture conditions, constitution of 1[4Cjpropionate incorporation activity in fibroblasts stimulated with 0.1-1.0 ,g/ml hydroxycobalamin, interallelic complementation with alleles bearing an R93H mutation, and an apparent K. (adenosylcobalamin) 1,000-fold higher than normal. These results demonstrate that the G717V mutation produces the mut-phenotype and localizes determinants for adenosylcobalamin binding near the carboxyl terminus of MCM. (J. Clin. Invest. 1992. 89:385-391.)

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Is there methylmalonyl CoA mutase in Aspergillus nidulans?

Cited by 17 publications

References 12 publications

Mitochondrial β‐oxidation in Aspergillus nidulans

Mitochondrial β‐oxidation in Aspergillus nidulans

Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis

Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria.

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