Artificial arrest of synthesis of pantothenate to inhibit growth of gamma proteobacteria

2014 Fiscal Year Final Research Report

• Project/Area Number: 25660068
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied microbiology
• Research Institution: National Institute of Genetics
• Principal Investigator: NIKI Hironri 国立遺伝学研究所, 系統生物研究センター, 教授 (70208122)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: パントテン酸 / 補酵素A

Outline of Final Research Achievements

Coenzyme A (CoA) is an ubiquitous and essential cofactor, synthesized from the precursor pantothenate. Vitamin biosynthetic pathways are normally tightly regulated, including the pathway from pantothenate to CoA. However, no regulation of pantothenate biosynthesis has been identified. We have recently described an additional component in the pantothenate biosynthetic pathway, PanZ, which promotes the activation of the zymogen, PanD, to form aspartate α-decarboxylase (ADC) in a CoA-dependent manner. Here we report the structure of PanZ in complex with PanD, which reveals the structural basis for the CoA dependence of this interaction and activation. In addition, we show that PanZ acts as a CoA-dependent inhibitor of ADC catalysis. This inhibitory effect can effectively regulate the biosynthetic pathway to pantothenate, and thereby also regulate CoA biosynthesis.

Free Research Field

微生物遺伝学