Construction of high level production system for anti-tubercular agent and anti-cancer drug by Escherichia coli

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08334
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Hiroshima University
• Principal Investigator: KUMAGAI Takanori 広島大学, 医系科学研究科(薬), 准教授 (70274058)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 抗結核薬 / D-サイクロセリン / 抗癌剤 / 異種生産 / ATP再生系 / ゲノム解析

Outline of Final Research Achievements

In the present study, production level of an anti-tubercular agent, D-cycloserine (D-CS), was improved by introducing a ATP regeneration system to the established D-CS production system using Escherichia coli. In addition, candidate genes of electron transfer system (ferredoxin and ferredoxin reductase) for DcsA, which is necessary for the synthesis of hydroxyurea (an intermediate of D-CS biosynthesis and an anti-cancer drug), were found by genome sequencing of a D-CS-producing microorganism.

Free Research Field

微生物薬品学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた成果により, 抗結核薬D-CSの大腸菌を宿主とした実用レベル高生産が達成できれば, より安全で安価なD-CSの供給につながる可能性があり, 意義があると考えられる。また, D-CS生産菌のゲノム解読は, 新規なアルギニン水酸化酵素の電子伝達系の解明, および, D-CS以外の新規化合物の発見につながる可能性があり, 学術的に意義があると考えられる。