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Amino acid biosynthetic pathways as targets for anti-fungal agents

Research Project

Project/Area Number 23659219
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bacteriology (including Mycology)
Research InstitutionChiba University

Principal Investigator

TOH-E Akio  千葉大学, 真菌医学研究センター, 客員教授 (90029249)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsCryptococcus neoformans / 含硫アミノ酸合成経路 / システイン合成酵素 / クリプトコックス / システイン合成系 / セリン経路 / セリンアセチル化酵素 / アミノ酸合成経路 / リジン合成経路 / システイン合成経路
Research Abstract

In contrast to the methionine biosynthetic pathway of Cryptococcus neoformans, that of cysteine remains largely unknown. Here we showed that C. neoformans produces cycteine solely by the serine pathway.We identified the gene encoding cysteine synthase and that encoding serine o-acetyl transferase. Each disruptant is viable and requires cysteine. We designated the gene for cystein synthase CYS1 and that for serine-o-acetly transferase CYS2. Methionine practically did not suppport the growth of the cys1D strain and cysteine did not support the growth of methione auxotroph met2D., indicating the both directions of the transsulfuration pathways are not functional in C. neoformans. This result placed C. neoformans in the unique. position concerning with sulfur amino acid metabolism. The cys1D strain lost pathogenicity against mice and mammals do not have cysteine synthase, indicating that cysteine synthase,serine-o-acetyltransferease as well, is a promizing candidate for drug development.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (2 results)

All 2011

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] Structural analysis of compounds withactions similar to local anesthetics andantipsychotic phenothiazines in yeast2011

    • Author(s)
      Yukifumi Uesono, Akio Toh-e, YoshikoKikuchi, Ichiro Terashima
    • Journal Title

      Yeast

      Volume: Volume 28 Issue: 5 Pages: 391-404

    • DOI

      10.1002/yea.1846

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] クリプトコックスにおけるリン酸代謝系2011

    • Author(s)
      東江昭夫、西沢正文、清水公徳、大楠美佐子、川本進
    • Organizer
      日本医真菌学会(招待講演)
    • Place of Presentation
      東京椿算山荘
    • Related Report
      2011 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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