Molecular Mechanism of Iron Sensing by HapX, the Master Regulator of Iron Homeostasis in Filamentous Fungi

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38020:Applied microbiology-related
• Research Institution: Meijo University
• Principal Investigator: KATO Masashi 名城大学, 農学部, 教授 (70242849)
• Co-Investigator(Kenkyū-buntansha): 志水 元亨 名城大学, 農学部, 准教授 (20423535)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 鉄の恒常性 / 糸状菌 / HapX / Aspergillus / 鉄硫黄クラスター / 転写因子

Outline of Final Research Achievements

HapX is the fungal-specific transcriptional regulator interacting with the wide domain transcription factor CCAAT-box binding protein (Hap complex), and plays an important role in iron homeostasis.
In this study, the following research was carried out using the model filamentous fungus Aspergillus nidulans. 1) Effects of mutagenesis into the three cysteine-rich regions (Crrs) present in the C-terminus on binding capacity of iron-sulfur (Fe/S) clusters. Analysis of spectra of the recombinant proteins was carried out to examine the contribution of each CCR. We found that HapX contained at least two iron-sulfur clusters. 2) In order to investigate the growth of wild and mutated HapX strains under iron depleted and repleted conditions, mutant strains in which the cysteine residues in the CRR were replaced with serine residues were constructed and growth was examined. We found that the first and second CCRs (CrrA and CrrB) were important for growth under iron depleted conditions.

Free Research Field

応用微生物学

Academic Significance and Societal Importance of the Research Achievements

本研究課題のカビの転写因子HapXが調節している酵素は、アコニターゼ（TCA回路）、チトクロームｃ（電子伝達系）、シスアコニターゼ（リジン合成）、カタラーゼ（酸化ストレス応答）、SreA（鉄取り込み系の転写抑制因子）など生理的に重要なものが多く、学術的に意義深い。さらに、病原性菌類や植物病原菌の病原性に関わることも知られており、研究成果は新規の抗真菌剤開発などの知的基盤になるなど、臨床医学、薬学、農薬学の分野でも役立つ。