Development of anti-malarial drugs targeting porphyrin biosynthesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25660088
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bioorganic chemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Wachi Masaaki 東京工業大学, 生命理工学研究科, 教授 (90192822)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アラレマイシン / 抗マラリア薬 / ポルフィリン / 5-アミノレブリン酸 / ポルフォビリノーゲン合成酵素 / hemA / ALAS

Outline of Final Research Achievements

Nineteen derivatives were synthesized using alaremycin as a lead compound. Heterologous expression systems were constructed with an E. coli hemB disruptant and PBGS genes derived from various organisms including malaria parasite. It was shown that sensitivity to alaremycin as well as its derivatives differ among these PBGSs.
Two genes encoding ALA synthase homologs, hemA and ALAS, were found in the genome sequence of the alaremycin producer strain Streptomyces sp. A012304. It was shown that the hemA gene was responsible for ALA biosynthesis by complementation test of an E. coli ALA auxotrophic mutant. On the other hand, it was revealed that the ALAS gene was involved in the biosynthesis of alaremycin together with its downstream three genes.

Free Research Field

応用微生物学