A chemical genomics approach for understanding chemical communication

2021 Fiscal Year Annual Research Report

• Project Area: Frontier research of chemical communications
• Project/Area Number: 17H06411
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: BOONE CHARLES 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (70601342)
• Co-Investigator(Kenkyū-buntansha): 八代田 陽子 国立研究開発法人理化学研究所, 環境資源科学研究センター, 副チームリーダー (60360658)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: chemical genomics / yeast / chemical communication

Outline of Annual Research Achievements

Using the S. cerevisiae chemical genomics (CG) analysis, we predicted a target of jervine. The yeast CG profile for jervine is the most similar to the one for D75-4590, a specific β-1,6-glucan biosynthesis inhibitor. A biochemical assay and yeast mutant analysis revealed that jervine inhibits the biosynthesis of β-1,6-glucan by acting on both Kre6 and Skn1. In addition to the the S. cerevisiae CG pipeline, we successfully established the S. pombe CG pipeline by constructing a barcoded deletion mutant library in a drug-hypersensitive background that consists of ~2,200 strains. Using this S. pombe system, we screened genes that conferred altered sensitivity to momilactone B (MB). The FYPO (the fission yeast phenotype ontology) term enrichment analysis indicated that the sensitized genes were involved in septum formation and we confirmed that S. pombe wild-type cells treated with MB showed abnormal morphology such as branched, elongated, and multiseptated cells with branch forming adjacent to septum. The data suggests MB affects septum formation and microtubule structure of fission yeast.
We continued to improve the method for a high-throughput human cell-based CG analysis using a cell suspension culture and established a workflow. We examined the bioactivity of several interesting bioactive compounds provided from the NPDepo library and from the group A02 in human HAP1 cells and conducted the CG analysis. For the compounds whose targets were successfully predicted by the yeast CG profiles, we assessed target prediction drawn from the human CG profiles.

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Toronto/The University of British Columbia(カナダ)
  • Country Name: CANADA
  • Counterpart Institution: University of Toronto/The University of British Columbia
• [Int'l Joint Research] University of Minnesota(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: University of Minnesota
• [Int'l Joint Research] ETH Zurich(スイス)
  • Country Name: SWITZERLAND
  • Counterpart Institution: ETH Zurich
• [Journal Article] Jerveratrum-type steroidal alkaloids inhibit β-1,6-glucan biosynthesis in fungal cell walls (2022)
  • Author(s): Kubo, K., Itto-Nakama, K., Ohnuki, S., Yashiroda, Y., Li, SC., Kimura, H., Kawamura, Y., Shimamoto, Y., Tominaga, KI., Yamanaka, D., Adachi, Y., Takashima, S., Noda, Y., Boone, C., Ohya, Y.
  • Journal Title: Microbiology Spectrum Volume: 10 Pages: e0087321
  • DOI: 10.1128/spectrum.00873-21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-throughput platform for yeast morphological profiling predicts the targets of bioactive compounds (2022)
  • Author(s): Ohnuki, S., Ogawa, I., Itto-Nakama, K., Lu, F., Ranjan, A., Kabbage, M., Gebre, AA., Yamashita, M., Li, SC., Yashiroda, Y., Yoshida, S., Usui, T., Piotrowski, JS., Andrews, BJ., Boone, C., Brown, GW., Ralph, J., Ohya, Y.
  • Journal Title: npj Systems Biology and Applications Volume: 8 Pages: 3
  • DOI: 10.1038/s41540-022-00212-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets (2021)
  • Author(s): Fu, C., Zhang, X., Veri, AO., Iyer, KR., Lash, E., Xue, A., Yan, H., Revie, NM., Wong, C., Lin, ZY., Polvi, EJ., Liston, SD., VanderSluis, B., Hou, J., Yashiroda, Y., Gingras, AC., Boone, C., O'Meara, TR., O'Meara, MJ., Noble, S., Robbins, N., Myers, CL., Cowen, LE.
  • Journal Title: Nature Communications Volume: 12 Pages: 6497
  • DOI: 10.1038/s41467-021-26850-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improving measures of chemical structural similarity using machine learning on chemical-genetic interactions (2021)
  • Author(s): Safizadeh, H., Simpkins, SW., Nelson, J., Li, SC., Piotrowski, JS., Yoshimura, M., Yashiroda, Y., Hirano, H., Osada, H., Yoshida, M., Boone, C., Myers, CL.
  • Journal Title: Journal of Chemical Information and Modeling Volume: 61 Pages: 4156-4172
  • DOI: 10.1021/acs.jcim.0c00993
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clionamines stimulate autophagy, inhibit Mycobacterium tuberculosis survival in macrophages, and target Pik1 (2021)
  • Author(s): Persaud, R., Li, SC., Chao, JD., Forestieri, R., Donohue, E., Balgi, AD., Zheng, X., Chao, JT., Yashiroda, Y., Yoshimura, M., Loewen, CJR., Gingras, AC., Boone, C., Av-Gay, Y., Roberge, M., Andersen, RJ.
  • Journal Title: Cell Chemical Biology Volume: - Pages: -
  • DOI: 10.1016/j.chembiol.2021.07.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genome-wide screening of genes associated with momilactone B sensitivity in the fission yeast Schizosaccharomyces pombe (2021)
  • Author(s): Tomita, K., Yashiroda, Y., Matsuo, Y., Piotrowski, JS., Li, SC., Okamoto, R., Yoshimura, M., Kimura, H., Kawamura, Y., Kawamukai, M., Boone, C., Yoshida, M., Nojiri, H., Okada, K.
  • Journal Title: G3 (Bethesda) Volume: 11 Pages: jkab156
  • DOI: 10.1093/g3journal/jkab156
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A genome-scale yeast library with inducible expression of individual genes (2021)
  • Author(s): Arita, Y., Kim, G., Li, Z., Friesen, H., Turco, G., Wang, RY., Climie, D., Usaj, M., Hotz, M., Stoops, EH., Baryshnikova, A., Boone, C., Botstein, D., Andrews, BJ., McIsaac, RS.
  • Journal Title: Molecular Systems Biology Volume: 17 Pages: e10207
  • DOI: 10.15252/msb.202110207
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Environmental robustness of the global yeast genetic interaction network (2021)
  • Author(s): Costanzo, M., Hou. J., Messier, V., Nelson, J., Rahman, M., VanderSluis, B., Wang, W., Pons, C., Ross, C., Usaj, M., San Luis, BJ., Shuteriqi, E., Koch, EN., Aloy, P., Myers, CL., Boone, C., Andrews, B.
  • Journal Title: Science Volume: 372 Pages: abf8424
  • DOI: 10.1126/science.abf8424
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 酵母の増殖阻害活性を示す含ホウ素化合物の作用機序解析 (2022)
  • Author(s): 八代田陽子、木村寛美、吉村麻美、臼井正哉、丹羽節、高橋一光、俣賀宣子、細谷孝充、Laurean Ilies、吉田稔、Charles Boone
  • Organizer: 日本農芸化学会2022年度大会
• [Presentation] 植物由来のジテルペン化合物Momilactone Bは細胞内のROSレベルを減少させることで細胞の増殖を阻害する (2022)
  • Author(s): 富田啓介、松尾安浩、八代田陽子、吉田稔、川向誠、野尻秀昭、岡田憲典
  • Organizer: 日本農芸化学会2022年度大会
• [Presentation] 奇数鎖脂肪酸による分裂酵母の脂質組成の攪乱および小胞体の形態異常 (2022)
  • Author(s): 星川陽次郎、西村慎一、松山晃久、Sheena Li、八代田陽子、Charles Boone、津川裕司、有田誠、吉田稔
  • Organizer: 日本農芸化学会2022年度大会
• [Presentation] 奇数鎖脂肪酸による分裂酵母の脂質代謝攪乱と細胞分裂阻害 (2021)
  • Author(s): 星川陽次郎、西村慎一、松山晃久、Sheena Li、八代田陽子、Charles Boone、津川裕司、有田誠、吉田稔
  • Organizer: 第63回日本脂質生化学会
• [Presentation] 奇数鎖脂肪酸は分裂酵母において細胞膜極性と細胞分裂に異常を引き起こす (2021)
  • Author(s): 星川陽次郎、西村慎一、松山晃久、Li Sheena、八代田陽子、Boone Charles、吉田稔
  • Organizer: 日本農芸化学会2021年度大会