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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Coenzyme A (CoA) is a well-known cofactor that plays an essential role in many metabolic reactions in all organisms. In Plasmodium falciparum, the most deadly among Plasmodium 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 (PfPanK1 and 2) in this parasite. Here we produced, purified, and biochemically characterized recombinant PfPanK1 for the first time. PfPanK1 showed activity using pantetheine besides pantothenate, as the primary substrate, indicating that CoA biosynthesis in the blood stage of P. falciparum can bypass pantothenate. We further developed a robust and reliable screening system to identify inhibitors using recombinant PfPanK1 and identified four PfPanK inhibitors from natural compounds.

Original languageEnglish
Article number639065
JournalFrontiers in cellular and infection microbiology
Volume11
DOIs
Publication statusPublished - 2021 Mar 9

Keywords

  • PfPanK1
  • PfPanK2
  • Plasmodium falciparum
  • coenzyme A
  • inhibitors

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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