Kynurenine aminotransferase activity of Aro8/Aro9 engage tryptophan degradation by producing kynurenic acid in Saccharomyces cerevisiae

Kazuto Ohashi, Romanas Chaleckis, Masak Takaine, Craig E. Wheelock, Satoshi Yoshida

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Kynurenic acid (KA) is a tryptophan (Trp) metabolite that is synthesised in a branch of kynurenine (KYN) pathway. KYN aminotransferase (KAT) catalyses deamination of KYN, yielding KA. Although KA synthesis is evolutionarily conserved from bacteria to humans, the cellular benefits of synthesising KA are unclear. In this study, we constructed a KAT-null yeast mutant defective in KA synthesis to clarify the cellular function of KA. Amino acid sequence analysis and LC/MS quantification of KA revealed that Aro8 and Aro9 are the major KATs. KA was significantly decreased in the aro8Δ aro9Δ double mutant. We found that aro8Δ aro9Δ cells did not exhibit obvious defects in growth or oxidative stress response when proper amounts of amino acids are supplied in the media. We further found that aro8Δ aro9Δ cells were sensitive to excess Trp. The Trp sensitivity was not rescued by addition of KA, suggesting that Trp sensitivity is not due to the loss of KA. In conclusion, we propose that KAT activity is required for detoxification of Trp by converting it to the less toxic KA.

Original languageEnglish
Article number12180
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

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kynurenine-oxoglutarate transaminase
Kynurenic Acid
Tryptophan
Saccharomyces cerevisiae
Kynurenine
Transaminases
Deamination

ASJC Scopus subject areas

  • General

Cite this

Kynurenine aminotransferase activity of Aro8/Aro9 engage tryptophan degradation by producing kynurenic acid in Saccharomyces cerevisiae. / Ohashi, Kazuto; Chaleckis, Romanas; Takaine, Masak; Wheelock, Craig E.; Yoshida, Satoshi.

In: Scientific Reports, Vol. 7, No. 1, 12180, 01.12.2017.

Research output: Contribution to journalArticle

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