AUTHOR=Nurkanto Arif , Jeelani Ghulam , Santos Herbert J. , Rahmawati Yulia , Mori Mihoko , Nakamura Yumi , Goto Kana , Saikawa Yoko , Annoura Takeshi , Tozawa Yuzuru , Sakura Takaya , Inaoka Daniel Ken , Shiomi Kazuro , Nozaki Tomoyoshi 

TITLE=Characterization of Plasmodium falciparum Pantothenate Kinase and Identification of Its Inhibitors From Natural Products

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.639065

DOI=10.3389/fcimb.2021.639065

ISSN=2235-2988

ABSTRACT=<p>Coenzyme A (CoA) is a well-known cofactor that plays an essential role in many metabolic reactions in all organisms. In <italic>Plasmodium falciparum</italic>, the most deadly among <italic>Plasmodium</italic> species that cause malaria, CoA and its biosynthetic pathway have been proven to be indispensable. The first and rate-limiting reaction in the CoA biosynthetic pathway is catalyzed by two putative pantothenate kinases (<italic>Pf</italic>PanK1 and 2) in this parasite. Here we produced, purified, and biochemically characterized recombinant <italic>Pf</italic>PanK1 for the first time. <italic>Pf</italic>PanK1 showed activity using pantetheine besides pantothenate, as the primary substrate, indicating that CoA biosynthesis in the blood stage of <italic>P. falciparum</italic> can bypass pantothenate. We further developed a robust and reliable screening system to identify inhibitors using recombinant <italic>Pf</italic>PanK1 and identified four <italic>Pf</italic>PanK inhibitors from natural compounds.</p>