Integrating yeast chemical genomics and mammalian cell pathway analysis

  • Acta Pharmacol Sin. 2019 Sep;40(9):1245-1255. doi: 10.1038/s41401-019-0231-y.
Fu-Lai Zhou   #  1  2 ,  Sheena C Li   #  3 ,  Yue Zhu  1  2 ,  Wan-Jing Guo  1  2 ,  Li-Jun Shao  1  2 ,  Justin Nelson  4 ,  Scott Simpkins  4 ,  De-Hua Yang  1 ,  Qing Liu  1 ,  Yoko Yashiroda  3 ,  Jin-Biao Xu  5 ,  Yao-Yue Fan  5 ,  Jian-Min Yue  5 ,  Minoru Yoshida  3  6  7 ,  Tian Xia  8 ,  Chad L Myers  9 ,  Charles Boone  10  11 ,  Ming-Wei Wang  12  13
Affiliations
  • 1. The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. RIKEN Center for Sustainable Resource Science, Wako, Saitama, 3510198, Japan.
  • 4. Bioinformatics and Computational Biology Program, University of Minnesota-Twin Cities, Minneapolis, Minnesota, 55455, USA.
  • 5. The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 6. Department of Biology, The University of Tokyo, Bunkyo-ku, Tokyo, 1138657, Japan.
  • 7. Collaborative Research for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo, 1138657, Japan.
  • 8. Department of Electronics and Information Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.
  • 9. Bioinformatics and Computational Biology Program, University of Minnesota-Twin Cities, Minneapolis, Minnesota, 55455, USA. [email protected].
  • 10. RIKEN Center for Sustainable Resource Science, Wako, Saitama, 3510198, Japan. [email protected].
  • 11. Donnelly Centre and Department of Molecular Genetics, University of Toronto, Ontario, M5S 3E1, Canada. [email protected].
  • 12. The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China. [email protected].
  • 13. University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  • # Contributed equally.
PMID: 31138898 DOI: 10.1038/s41401-019-0231-y
Abstract

Chemical genomics has been applied extensively to evaluate small molecules that modulate biological processes in Saccharomyces cerevisiae. Here, we use yeast as a surrogate system for studying compounds that are active against metazoan targets. Large-scale chemical-genetic profiling of thousands of synthetic and natural compounds from the Chinese National Compound Library identified those with high-confidence bioprocess target predictions. To discover compounds that have the potential to function like therapeutic agents with known targets, we also analyzed a reference library of approved drugs. Previously uncharacterized compounds with chemical-genetic profiles resembling existing drugs that modulate Autophagy and Wnt/β-catenin signal transduction were further examined in mammalian cells, and new modulators with specific modes of action were validated. This analysis exploits yeast as a general platform for predicting compound bioactivity in mammalian cells.

Keywords
Wnt/β-catenin signaling pathway; autophagy; chemical genomics; tubulin cytoskeleton assembly; yeast.
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