Mode of action study of a novel antituberculous agent CPZEN-45

2015 Fiscal Year Final Research Report

• Project/Area Number: 26870829
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology); Applied biochemistry
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: ISHIZAKI Yoshimasa 公益財団法人微生物化学研究会, 微生物化学研究所, 主任研究員 (10414103)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 作用機序の同定

Outline of Final Research Achievements

In this research, I tried to identify the primary target of CPZEN-45, which is a promising anti tubercular agent derivatized from natural product caprazamycins. At the beginning of this research, I focused on following three candidate enzymes for the target; (1) MurX which is a target of caprazamycins and involved in peptidoglycan biosynthesis, (2) WecA which is a paralog of MurX and involved in biosynthesis of arabinogalactan (AG), and (3) AG ligase, which has similar function to MurX and WecA.
As the result of this research, it is revealed that CPZEN-45 inhibited the activity of WecA and de novo synthesis of AG. In contrast, CPZEN-45 did not inhibit the activity of MurX, which is a primary target of caprazamycins. These results indicated that CPZEN-45 showed antituberculous activity by inhibiting WecA enzyme and subsequent blocking of AG biosynthesis.
Also, my collaborator and I succeeded to identify AG ligase, which we expected to be a candidate of target of CPZEN-45.

Free Research Field

微生物の遺伝学