Purine auxotrophy: Possible applications beyond genetic marker

Agnese Kokina, Zane Ozolina, Janis Liepins (Coresponding Author)

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Exploring new drug candidates or drug targets against many illnesses is necessary as “traditional” treatments lose their effectivity. Cancer and sicknesses caused by protozoan parasites are among these diseases. Cell purine metabolism is an important drug target. Theoretically, inhibiting purine metabolism could stop the proliferation of unwanted cells. Purine metabolism is similar across all eukaryotes. However, some medically important organisms or cell lines rely on their host purine metabolism. Protozoans causing malaria, leishmaniasis, or toxoplasmosis are purine auxotrophs. Some cancer forms have also lost the ability to synthesize purines de novo. Budding yeast can serve as an effective model for eukaryotic purine metabolism, and thus, purine auxotrophic strains could be an important tool. In this review, we present the common principles of purine metabolism in eukaryotes, effects of purine starvation in eukaryotic cells, and purine-starved Saccharomyces cerevisiae as a model for purine depletion-elicited metabolic states with applications in evolution studies and pharmacology. Purine auxotrophic yeast strains behave differently when growing in media with sufficient supplementation with adenine or in media depleted of adenine (starvation). In the latter, they undergo cell cycle arrest at G1/G0 and become stress resistant. Importantly, similar effects have also been observed among parasitic protozoans or cancer cells. We consider that studies on metabolic changes caused by purine auxotrophy could reveal new options for parasite or cancer therapy. Further, knowledge on phenotypic changes will improve the use of auxotrophic strains in high-throughput screening for primary drug candidates.

Original languageEnglish
Pages (from-to)649-656
Number of pages8
JournalYeast
Volume36
Issue number11
DOIs
Publication statusPublished - 1 Nov 2019
Externally publishedYes

Keywords*

  • budding yeast
  • cancer
  • evolution model
  • malaria
  • purine auxotrophy
  • Saccharomyces cerevisiae

Field of Science*

  • 1.6 Biological sciences

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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