Mutants of Neurospora Deficient in d-Amino Acid Oxidase

Ohnishi, Eiji; Macleod, Helen; Horowitz, N. H.

doi:10.1016/s0021-9258(18)81376-x

Cited by 27 publications

(4 citation statements)

References 13 publications

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“…These included genes involved in glycine metabolism such as gly-3 (NCU02727), gyd-1 (NCU02475), oxD (NCU06558), and NCU03761 but also genes involved in the metabolism of a variety of other amino acids (Fig. 2B and Dataset S1) (26). This result may indicate that since cells rarely see glycine in isolation from other amino acids, the presence of glycine activated expression of genes involved in a variety of amino acid utilization pathways.…”

Section: Resultsmentioning

confidence: 97%

DNA affinity purification sequencing and transcriptional profiling reveal new aspects of nitrogen regulation in a filamentous fungus

Huberman

Kowbel

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Sensing available nutrients and efficiently utilizing them is a challenge common to all organisms. The model filamentous fungus Neurospora crassa is capable of utilizing a variety of inorganic and organic nitrogen sources. Nitrogen utilization in N. crassa is regulated by a network of pathway-specific transcription factors that activate genes necessary to utilize specific nitrogen sources in combination with nitrogen catabolite repression regulatory proteins. We identified an uncharacterized pathway-specific transcription factor, amn-1, that is required for utilization of the nonpreferred nitrogen sources proline, branched-chain amino acids, and aromatic amino acids. AMN-1 also plays a role in regulating genes involved in responding to the simple sugar mannose, suggesting an integration of nitrogen and carbon metabolism. The utilization of nonpreferred nitrogen sources, which require metabolic processing before being used as a nitrogen source, is also regulated by the nitrogen catabolite regulator NIT-2. Using RNA sequencing combined with DNA affinity purification sequencing, we performed a survey of the role of NIT-2 and the pathway-specific transcription factors NIT-4 and AMN-1 in directly regulating genes involved in nitrogen utilization. Although previous studies suggested promoter binding by both a pathway-specific transcription factor and NIT-2 may be necessary for activation of nitrogen-responsive genes, our data show that pathway-specific transcription factors regulate genes involved in the catabolism of specific nitrogen sources, while NIT-2 regulates genes involved in utilization of all nonpreferred nitrogen sources, such as nitrogen transporters. Together, these transcription factors form a nutrient sensing network that allows N. crassa cells to regulate nitrogen utilization.

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Section: Resultsmentioning

confidence: 97%

DNA affinity purification sequencing and transcriptional profiling reveal new aspects of nitrogen regulation in a filamentous fungus

Huberman

Kowbel

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Similar conclusions were drawn for D-amino acid oxidase of mold, Neurospora crassa. OHNISHI, MACLEOD and HOROWITZ (1962) isolated several mutants lacking this enzyme activity and examined their growth and fertility. They could not find significant differences between these mutants and the wild-type strain.…”

Section: Discussionmentioning

confidence: 99%

MOUSE MUTANT DEFICIENT IN d-AMINO ACID OXIDASE ACTIVITY

1983

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d-Amino acid oxidase activity in the kidney homogenates of mice of seven strains was measured to search for a mutant for this enzyme. There was a consistent sex difference in the enzyme activity in these strains: male mice showed higher levels of the enzyme activity than females. In contrast to other strains, some mice of the ddY strain did not possess enzyme activity. This trait was inheritable, and a mouse stock without enzyme activity (DAO-) was established. The allele (Dao-1c) carried by the DAO- mice was recessive and behaved as a single autosomal gene in inheritance. Heterozygous mice for this gene (Dao-1 +/Dao-1c) showed nearly half the enzyme activity of the wild-type homozygotes (Dao-1 +/Dao-1 +), suggesting that Dao-1c is a null allele and that there is a gene dosage effect on the enzyme activity.

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“…The physiological relevance of DAOs has diversified across organisms harboring the gene. Limited by the analytical techniques, it was earlier thought that DAAs are present in prokaryotes and some eukaryotes including worms and insects, but absent in higher multicellular organisms. , In fungi, the enzymatic breakdown of DAAs supports their growth on certain DAAs as the sole source of carbon, nitrogen, and energy, and in the case of d -methionine, as a source of sulfur as well . With the advent of improved analytical methods such as HPLC, several studies in the latter half of the 20th century reported the presence of appreciable amounts of DAAs in invertebrates, marine animals, and mammalian tissues.…”

Section: L-amino Acid Oxidases (Laos or Laaos) And D-amino Acid Oxida...mentioning

confidence: 99%

“…62 , 8 In fungi, the enzymatic breakdown of DAAs supports their growth on certain DAAs as the sole source of carbon, nitrogen, and energy, and in the case of d -methionine, as a source of sulfur as well. 63 With the advent of improved analytical methods such as HPLC, several studies in the latter half of the 20th century reported the presence of appreciable amounts of DAAs in invertebrates, marine animals, and mammalian tissues. Hence, studies on the physiological relevance of DAOs in metazoans were initiated in the 1980s.…”

Section: -Amino Acid Oxidases (Laos or Laaos) And D ...mentioning

confidence: 99%

Amino Acid Chirality: Stereospecific Conversion and Physiological Implications

Das,

Balaram,

Sanyal

2024

ACS Omega

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The absolute configuration dictates the biological role of chiral molecules in the living world. This is best exemplified by all ribosomally synthesized polypeptides having chiral amino acids only in the L-configuration. However, D-amino acids are also associated with various vital biological processes such as peptidoglycan of the bacterial cell wall, ligands for neurotransmitters, molecules involved in signaling, and precursors of metabolites, to name a few. The occurrence of both L-and D-enantiomers of amino acids in the living systems necessitates the presence of enzymes that exhibit stereoselectivity in recognition of substrates. This minireview summarizes the overall mechanistic insights into the interconversion of L-and D-amino acids by the amino acid racemases. We discuss the structural, mechanistic, and evolutionary relationship of four crucial enzymes that catalyze the oxidative deamination of L-or D-amino acids and their physiological role in microbes and higher organisms. We highlight the physiological implications of D-amino acid oxidase and D-aspartate oxidase in human health and diseases and their applications as drug targets. Finally, we summarize the potential applications of microbially obtained chiral-selective enzymes as biocatalysts and for various industrial purposes.

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Mutants of Neurospora Deficient in d-Amino Acid Oxidase

Cited by 27 publications

References 13 publications

DNA affinity purification sequencing and transcriptional profiling reveal new aspects of nitrogen regulation in a filamentous fungus

DNA affinity purification sequencing and transcriptional profiling reveal new aspects of nitrogen regulation in a filamentous fungus

MOUSE MUTANT DEFICIENT IN d-AMINO ACID OXIDASE ACTIVITY

Amino Acid Chirality: Stereospecific Conversion and Physiological Implications

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