Amino acid biosynthetic pathways as targets for anti-fungal agents

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659219
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including Mycology)
• Research Institution: Chiba 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
• Keywords: Cryptococcus neoformans / 含硫アミノ酸合成経路 / システイン合成酵素

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.